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Alzheimer Disease: HELP
Articles from Chandigarh
Based on 77 articles published since 2010
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These are the 77 published articles about Alzheimer Disease that originated from Chandigarh during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Review Lifestyle Modifications and Nutritional Interventions in Aging-Associated Cognitive Decline and Alzheimer's Disease. 2019

Bhatti, Gurjit Kaur / Reddy, Arubala P / Reddy, P Hemachandra / Bhatti, Jasvinder Singh. ·Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Mohali, India. · Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, United States. · Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, United States. · Neuroscience and Pharmacology, Texas Tech University Health Sciences Center, Lubbock, TX, United States. · Neurology, Departments of School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, United States. · Public Health Department of Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX, United States. · Speech, Language and Hearing Sciences Department, School Health Professions, Texas Tech University Health Sciences Center, Lubbock, TX, United States. · Department of Biotechnology and Microbial Biotechnology, Sri Guru Gobind Singh College, Chandigarh, India. ·Front Aging Neurosci · Pubmed #31998117.

ABSTRACT: Alzheimer's disease (AD) is a type of incurable neurodegenerative disease that is characterized by the accumulation of amyloid-β (Aβ; plaques) and tau hyperphosphorylation as neurofibrillary tangles (NFTs) in the brain followed by neuronal death, cognitive decline, and memory loss. The high prevalence of AD in the developed world has become a major public health challenge associated with social and economic burdens on individuals and society. Due to there being limited options for early diagnosis and determining the exact pathophysiology of AD, finding effective therapeutic strategies has become a great challenge. Several possible risk factors associated with AD pathology have been identified; however, their roles are still inconclusive. Recent clinical trials of the drugs targeting Aβ and tau have failed to find a cure for the AD pathology. Therefore, effective preventive strategies should be followed to reduce the exponential increase in the prevalence of cognitive decline and dementia, especially AD. Although the search for new therapeutic targets is a great challenge for the scientific community, the roles of lifestyle interventions and nutraceuticals in the prevention of many metabolic and neurodegenerative diseases are highly appreciated in the literature. In this article, we summarize the molecular mechanisms involved in AD pathology and the possible ameliorative action of lifestyle and nutritional interventions including diet, exercise, Calorie restriction (CR), and various bioactive compounds on cognitive decline and dementia. This article will provide insights into the role of non-pharmacologic interventions in the modulation of AD pathology, which may offer the benefit of improving quality of life by reducing cognitive decline and incident AD.

2 Review Rollercoaster ride of kynurenines: steering the wheel towards neuroprotection in Alzheimer's disease. 2018

Sharma, Radhika / Razdan, Karan / Bansal, Yashika / Kuhad, Anurag. ·a Pharmacology Research Laboratory , University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University , Chandigarh , India. · b Pharmaceutics division , University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University , Chandigarh , India. ·Expert Opin Ther Targets · Pubmed #30223691.

ABSTRACT: INTRODUCTION: Alzheimer's disease (AD) is associated with cerebral cognitive deficits exhibiting two cardinal hallmarks: accruement of extracellular amyloid plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. The currently accessible therapeutic armamentarium merely provides symptomatic relief. Therefore, the cry for prospective neuroprotective strategies seems to be the need of the hour. Areas covered: This review comprehensively establishes correlation between kynurenine pathway (KP) metabolites and AD with major emphasis on its two functionally contrasting neuroactive metabolites i.e. kynurenic acid (KYNA) and quinolinic acid (QUIN) and enlists various clinical studies which hold a potential for future therapeutics in AD. Also, major hypotheses of AD and mechanisms underlying them have been scrutinized with the aim to brush up the readers with basic pathology of AD. Expert opinion: KP is unique in itself as it holds two completely different domains i.e. neurotoxic QUIN and neuroprotective KYNA and disrupted equilibrium between the two has a hand in neurodegeneration. KYNA has long been demonstrated to be neuroprotective but lately being disparaged for cognitive side effects. But we blaze a trail by amalgamating the pharmacological mechanistic studies of KYNA in kinship with α7nAChRs, NMDARs and GABA which lends aid in favour of KA.

3 Review Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer's Disease. 2018

Reddy, P Hemachandra / Manczak, Maria / Yin, Xiangling / Grady, Mary Catherine / Mitchell, Andrew / Tonk, Sahil / Kuruva, Chandra Sekhar / Bhatti, Jasvinder Singh / Kandimalla, Ramesh / Vijayan, Murali / Kumar, Subodh / Wang, Rui / Pradeepkiran, Jangampalli Adi / Ogunmokun, Gilbert / Thamarai, Kavya / Quesada, Kandi / Boles, Annette / Reddy, Arubala P. ·Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, USA. · Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX, USA. · Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, USA. · Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX, USA. · Speech, Language and Hearing Sciences, Texas Tech University Health Sciences Center, Lubbock, TX, USA. · Department of Public Health, Graduate School of Biomedical Studies, Texas Tech University Health Sciences Center, Lubbock, TX, USA. · Department of Biotechnology and Bioinformatics, Sri Guru Gobind Singh College, Chandigarh, India. · Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA. ·J Alzheimers Dis · Pubmed #29332042.

ABSTRACT: The purpose of our article is to assess the current understanding of Indian spice, curcumin, against amyloid-β (Aβ)-induced toxicity in Alzheimer's disease (AD) pathogenesis. Natural products, such as ginger, curcumin, and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes, and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions. In the last decade, several groups have designed and synthesized curcumin and its derivatives and extensively tested using cell and mouse models of AD. Recent research on Aβ and curcumin has revealed that curcumin prevents Aβ aggregation and crosses the blood-brain barrier, reach brain cells, and protect neurons from various toxic insults of aging and Aβ in humans. Recent research has also reported that curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD. Further, recent groups have initiated studies on elderly individuals and patients with AD and the outcome of these studies is currently being assessed. This article highlights the beneficial effects of curcumin on AD. This article also critically assesses the current limitations of curcumin's bioavailability and urgent need for new formulations to increase its brain levels to treat patients with AD.

4 Review Cracking novel shared targets between epilepsy and Alzheimer's disease: need of the hour. 2018

Garg, Nitika / Joshi, Rupa / Medhi, Bikash. ·Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 1600142, Punjab, India. · Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 1600142, Punjab, India, e-mail:drbikashus@yahoo.com. ·Rev Neurosci · Pubmed #29329108.

ABSTRACT: Epilepsy and Alzheimer's disease (AD) are interconnected. It is well known that seizures are linked with cognitive impairment, and there are various shared etiologies between epilepsy and AD. The connection between hyperexcitability of neurons and cognitive dysfunction in the progression of AD or epileptogenesis plays a vital role for improving selection of treatment for both diseases. Traditionally, seizures occur less frequently and in later stages of age in patients with AD which in turn implies that neurodegeneration causes seizures. The role of seizures in early stages of pathogenesis of AD is still an issue to be resolved. So, it is well timed to analyze the common pathways involved in pathophysiology of AD and epilepsy. The present review focuses on similar potential underlying mechanisms which may be related to the causes of seizures in epilepsy and cognitive impairment in AD. The proposed review will focus on many possible newer targets like abnormal expression of various enzymes like GSK-3β, PP2A, PKC, tau hyperphosphorylation, MMPs, caspases, neuroinflammation and oxidative stress associated with number of neurodegenerative diseases linked with epilepsy. The brief about the prospective line of treatment of both diseases will also be discussed in the present review.

5 Review Exploring the potential of natural and synthetic neuroprotective steroids against neurodegenerative disorders: A literature review. 2018

Bansal, Ranju / Singh, Ranjit. ·University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India. ·Med Res Rev · Pubmed #28697282.

ABSTRACT: Neurodegeneration is a complex process, which leads to progressive brain damage due to loss of neurons. Despite exhaustive research, the cause of neuronal loss in various degenerative disorders is not entirely understood. Neuroprotective steroids constitute an important line of attack, which could play a major role against the common mechanisms associated with various neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Natural endogenous steroids induce the neuroprotection by protecting the nerve cells from neuronal injury through multiple mechanisms, therefore the structural modifications of the endogenous steroids could be helpful in the generation of new therapeutically useful neuroprotective agents. The review article will keep the readers apprised of the detailed description of natural as well as synthetic neuroprotective steroids from the medicinal chemistry point of view, which would be helpful in drug discovery efforts aimed toward neurodegenerative diseases.

6 Review Molecular Links and Biomarkers of Stroke, Vascular Dementia, and Alzheimer's Disease. 2017

Vijayan, M / Kumar, S / Bhatti, J S / Reddy, P H. ·Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States. Electronic address: murali.vijayan@ttuhsc.edu. · Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States. · Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States; Department of Biotechnology, Sri Guru Gobind Singh College, Chandigarh, India. · Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States; Texas Tech University Health Sciences Center, Lubbock, TX, United States. ·Prog Mol Biol Transl Sci · Pubmed #28253992.

ABSTRACT: Stroke is a very common neurological disease, and it occurs when the blood supply to part of the brain is interrupted and the subsequent shortage of oxygen and nutrients causes damage to the brain tissue. Stroke is the second leading cause of death and the third leading cause of disability-adjusted life years. The occurrence of stroke increases with age, but anyone at any age can suffer a stroke. Stroke can be broadly classified in two major clinical types: ischemic stroke (IS) and hemorrhagic stroke. Research also revealed that stroke, vascular dementia (VaD), and Alzheimer's disease (AD) increase with a number of modifiable factors, and most strokes can be prevented and/or controlled through pharmacological or surgical interventions and lifestyle changes. The pathophysiology of stroke, VaD, and AD is complex, and recent molecular and postmortem brain studies have revealed that multiple cellular changes have been implicated, including inflammatory responses, microRNA alterations, and marked changes in brain proteins. These molecular and cellular changes provide new information for developing therapeutic strategies for stroke and related vascular disorders treatment. IS is the major risk factor for VaD and AD. This chapter summarizes the (1) links among stroke-VaD-AD; (2) updates the latest developments of research in identifying protein biomarkers in peripheral and central nervous system tissues; and (3) critically evaluates miRNA profile and function in human blood samples, animal, and postmortem brains.

7 Review MicroRNAs as Peripheral Biomarkers in Aging and Age-Related Diseases. 2017

Kumar, S / Vijayan, M / Bhatti, J S / Reddy, P H. ·Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States. Electronic address: subodh.kumar@ttuhsc.edu. · Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States. · Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States; Department of Biotechnology, Sri Guru Gobind Singh College, Chandigarh, India. · Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States; Texas Tech University Health Sciences Center, Lubbock, TX, United States. ·Prog Mol Biol Transl Sci · Pubmed #28253991.

ABSTRACT: MicroRNAs (miRNAs) are found in the circulatory biofluids considering the important molecules for biomarker study in aging and age-related diseases. Blood or blood components (serum/plasma) are primary sources of circulatory miRNAs and can release these in cell-free form either bound with some protein components or encapsulated with microvesicle particles, called exosomes. miRNAs are quite stable in the peripheral circulation and can be detected by high-throughput techniques like qRT-PCR, microarray, and sequencing. Intracellular miRNAs could modulate mRNA activity through target-specific binding and play a crucial role in intercellular communications. At a pathological level, changes in cellular homeostasis lead to the modulation of molecular function of cells; as a result, miRNA expression is deregulated. Deregulated miRNAs came out from cells and frequently circulate in extracellular body fluids as part of various human diseases. Most common aging-associated diseases are cardiovascular disease, cancer, arthritis, dementia, cataract, osteoporosis, diabetes, hypertension, and neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Variation in the miRNA signature in a diseased peripheral circulatory system opens up a new avenue in the field of biomarker discovery. Here, we measure the biomarker potential of circulatory miRNAs in aging and various aging-related pathologies. However, further more confirmatory researches are needed to elaborate these findings at the translation level.

8 Review MicroRNAs, Aging, Cellular Senescence, and Alzheimer's Disease. 2017

Reddy, P H / Williams, J / Smith, F / Bhatti, J S / Kumar, S / Vijayan, M / Kandimalla, R / Kuruva, C S / Wang, R / Manczak, M / Yin, X / Reddy, A P. ·Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States; Texas Tech University Health Sciences Center, Lubbock, TX, United States. Electronic address: hemachandra.reddy@ttuhsc.edu. · Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States. · Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States; Department of Biotechnology, Sri Guru Gobind Singh College, Chandigarh, India. · Texas Tech University Health Sciences Center, Lubbock, TX, United States. ·Prog Mol Biol Transl Sci · Pubmed #28253983.

ABSTRACT: Aging is a normal process of living being. It has been reported that multiple cellular changes, including oxidative damage/mitochondrial dysfunction, telomere shortening, inflammation, may accelerate the aging process, leading to cellular senescence. These cellular changes induce age-related human diseases, including Alzheimer's, Parkinson's, multiple sclerosis, amyotrophic lateral sclerosis, cardiovascular, cancer, and skin diseases. Changes in somatic and germ-line DNA and epigenetics are reported to play large roles in accelerating the onset of human diseases. Cellular mechanisms of aging and age-related diseases are not completely understood. However, recent discoveries in molecular biology have revealed that microRNAs (miRNAs) are potential indicators of aging, cellular senescence, and Alzheimer's disease (AD). The purpose of our chapter is to highlight recent advancements in miRNAs and their involvement in cellular changes in aging, cellular senescence, and AD. This chapter also critically evaluates miRNA-based therapeutic drug targets for aging and age-related diseases, particularly Alzheimer's.

9 Review Potential for Stem Cells Therapy in Alzheimer's Disease: Do Neurotrophic Factors Play Critical Role? 2017

Bali, Parul / Lahiri, Debomoy K / Banik, Avijit / Nehru, Bimla / Anand, Akshay. ·Neuroscience Research Lab, Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. ·Curr Alzheimer Res · Pubmed #26971940.

ABSTRACT: Alzheimer's disease (AD) is one of the most common causes of dementia. Despite several decades of research in AD, there is no standard disease- modifying therapy available and currentlyapproved drugs provide only symptomatic relief. Stem cells hold immense potential to regenerate damaged tissues and are currently tested in some brain-related disorders, such as AD, amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). We review stem cell transplantation studies using preclinical and clinical tools. We describe different sources of stem cells used in various animal models and explaining the putative molecular mechanisms that can rescue neurodegenerative disorders. The clinical studies suggest safety, efficacy and translational potential of stem cell therapy. The therapeutic outcome of stem cell transplantation has been promising in many studies, but no unifying hypothesis can convincingly explain the underlying mechanism. Some studies have reported paracrine effects exerted by these stem cells via the release of neurotrophic factors, while other studies describe the immunomodulatory effects exerted by the transplanted cells. There are also reports which indicate that stem cell transplantation might result in endogenous cell proliferation or replacement of diseased cells. In animal models of AD, stem cell transplantation is also believed to increase expression of synaptic proteins.

10 Review Current pharmacotherapy and putative disease-modifying therapy for Alzheimer's disease. 2016

Kulshreshtha, Akanksha / Piplani, Poonam. ·University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India. · University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India. ppvohra28in@yahoo.co.in. ·Neurol Sci · Pubmed #27250365.

ABSTRACT: Alzheimer's disease (AD) is an age-related neurodegenerative disease of the central nervous system correlated with the progressive loss of cognition and memory. β-Amyloid plaques, neurofibrillary tangles and the deficiency in cholinergic neurotransmission constitute the major hallmarks of the AD. Two major hypotheses have been implicated in the pathogenesis of AD namely the cholinergic hypothesis which ascribed the clinical features of dementia to the deficit cholinergic neurotransmission and the amyloid cascade hypothesis which emphasized on the deposition of insoluble peptides formed due to the faulty cleavage of the amyloid precursor protein. Current pharmacotherapy includes mainly the acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor agonist which offer symptomatic therapy and does not address the underlying cause of the disease. The disease-modifying therapy has garnered a lot of research interest for the development of effective pharmacotherapy for AD. β and γ-Secretase constitute attractive targets that are focussed in the disease-modifying approach. Potentiation of α-secretase also seems to be a promising approach towards the development of an effective anti-Alzheimer therapy. Additionally, the ameliorative agents that prevent aggregation of amyloid peptide and also the ones that modulate inflammation and oxidative damage associated with the disease are focussed upon. Development in the area of the vaccines is in progress to combat the characteristic hallmarks of the disease. Use of cholesterol-lowering agents also is a fruitful strategy for the alleviation of the disease as a close association between the cholesterol and AD has been cited. The present review underlines the major therapeutic strategies for AD with focus on the new developments that are on their way to amend the current therapeutic scenario of the disease.

11 Review Understanding Aspects of Aluminum Exposure in Alzheimer's Disease Development. 2016

Kandimalla, Ramesh / Vallamkondu, Jayalakshmi / Corgiat, Edwin B / Gill, Kiran Dip. ·Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India. · Radiation Oncology, Emory University, Atlanta, GA. · Department of Physics, National Institute of Technology, Warangal, Telangana, India. · Genetics and Molecular Biology Program, Emory University Laney Graduate School, Atlanta, GA. ·Brain Pathol · Pubmed #26494454.

ABSTRACT: Aluminum is a ubiquitously abundant nonessential element. Aluminum has been associated with neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis, and dialysis encephalopathy. Many continue to regard aluminum as controversial although increasing evidence supports the implications of aluminum in the pathogenesis of AD. Aluminum causes the accumulation of tau protein and Aβ protein in the brain of experimental animals. Aluminum induces neuronal apoptosis in vivo and in vitro, either by endoplasmic stress from the unfolded protein response, by mitochondrial dysfunction, or a combination of them. Some, people who are exposed chronically to aluminum, either from through water and/or food, have not shown any AD pathology, apparently because their gastrointestinal barrier is more effective. This article is written keeping in mind mechanisms of action of aluminum neurotoxicity with respect to AD.

12 Review Molecular and biochemical trajectories from diabetes to Alzheimer's disease: A critical appraisal. 2015

Sandhir, Rajat / Gupta, Smriti. ·Rajat Sandhir, Smriti Gupta, Department of Biochemistry, Panjab University, Chandigarh 160014, India. ·World J Diabetes · Pubmed #26464760.

ABSTRACT: Diabetes mellitus (DM), a metabolic disorder is a major orchestra influencing brain and behavioral responses via direct or indirect mechanisms. Many lines of evidence suggest that diabetic patients apparently face severe brain complications, but the story is far from being fully understood. Type 2 diabetes, an ever increasing epidemic and its chronic brain complications are implicated in the development of Alzheimer's disease (AD). Evidences from clinical and experimental studies suggest that insulin draws a clear trajectory from the peripheral system to the central nervous system. This review is a spot light on striking pathological, biochemical, molecular and behavioral commonalities of AD and DM. Incidence of cognitive decline in diabetic patients and diabetic symptoms in AD patients has brought the concept of brain diabetes to attention. Brain diabetes reflects insulin resistant brain state with oxidative stress, cognitive impairment, activation of various inflammatory cascade and mitochondrial vulnerability as a shared footprint of AD and DM. It has become extremely important for the investigators to understand the patho-physiology of brain complications in diabetes and put intensive pursuits for therapeutic interventions. Although, decades of research have yielded a range of molecules with potential beneficial effects, but they are yet to meet the expectations.

13 Review A review on mitochondrial restorative mechanism of antioxidants in Alzheimer's disease and other neurological conditions. 2015

Kumar, Anil / Singh, Arti. ·Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University , Chandigarh, India. ·Front Pharmacol · Pubmed #26441662.

ABSTRACT: Neurodegenerative diseases are intricate in nature because of the involvement of the multiple pathophysiological events including mitochondrial dysfunction, neuroinflammation and oxidative stress. Alzheimer's disease (AD) is a neurodegenerative disease explained by extracellular amyloid β deposits, intracellular neurofibrillary tangles and mitochondrial dysfunction. Increasing evidence has indicated that mitochondrial dysfunction displays significant role in the pathophysiological processes of AD. Mitochondrial dysfunction involves alterations in mitochondrial respiratory enzyme complex activities, oxidative stress, opening of permeability transition pore, and enhanced apoptosis. Various bioenergetics and antioxidants have been tried or under different investigational phase against AD and other neurodegenerative disorders (Parkinson's disease, Huntington's disease, and Amyotrophic lateral sclerosis) because of their complex and multiple site of action. These mitochondrial-targeting bioenergetics and antioxidant compounds such as coenzyme Q10, idebenone, creatine, mitoQ, mitovitE, MitoTEMPOL, latrepirdine, methylene blue, triterpenoids, SS peptides, curcumin, Ginkgo biloba, and omega-3 polyunsaturated fatty acids with potential efficacy in AD have been identified. Present review is intent to discuss mitochondrial restorative mechanisms of these bioenergetics and antioxidants as a potential alternative drug strategy for effective management of AD.

14 Review Translation of Pre-Clinical Studies into Successful Clinical Trials for Alzheimer's Disease: What are the Roadblocks and How Can They Be Overcome? 2015

Banik, Avijit / Brown, Richard E / Bamburg, James / Lahiri, Debomoy K / Khurana, Dheeraj / Friedland, Robert P / Chen, Wei / Ding, Ying / Mudher, Amritpal / Padjen, Ante L / Mukaetova-Ladinska, Elizabeta / Ihara, Masafumi / Srivastava, Sudhir / Padma Srivastava, M V / Masters, Colin L / Kalaria, Raj N / Anand, Akshay. ·Neuroscience Research Lab, Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. · Department of Psychology and Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada. · Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA. · Departments of Psychiatry and of Medical & Molecular Genetics, Indiana University School of Medicine, Neuroscience Research Center, Indianapolis, IN, USA. · Department of Neurology, University of Louisville, School of Medicine, Louisville, KY, USA. · Division of Pulmonary Medicine, Allergy and Immunology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA. · Department of Biostatistics, University of Pittsburgh, 318C Parran Hall, Pittsburgh, PA, USA. · Southampton Neurosciences Group, University of Southampton, Southampton, UK. · Department of Pharmacology & Therapeutics, McGill University, Montreal, QC, Canada. · Institute of Neuroscience, Newcastle University, NIHR Biomedical Research Building, Campus for Ageing and Vitality, Newcastle upon Tyne, UK. · Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan. · Division of Toxicology, Central Drug Research Institute, Lucknow, India. · Department of Neurology, Neurosciences Centre, All India Institute of Medical Sciences, New Delhi, India. · Mental Health Research Institute, University of Melbourne, Royal Parade, The VIC, Australia. ·J Alzheimers Dis · Pubmed #26401762.

ABSTRACT: Preclinical studies are essential for translation to disease treatments and effective use in clinical practice. An undue emphasis on single approaches to Alzheimer's disease (AD) appears to have retarded the pace of translation in the field, and there is much frustration in the public about the lack of an effective treatment. We critically reviewed past literature (1990-2014), analyzed numerous data, and discussed key issues at a consensus conference on Brain Ageing and Dementia to identify and overcome roadblocks in studies intended for translation. We highlight various factors that influence the translation of preclinical research and highlight specific preclinical strategies that have failed to demonstrate efficacy in clinical trials. The field has been hindered by the domination of the amyloid hypothesis in AD pathogenesis while the causative pathways in disease pathology are widely considered to be multifactorial. Understanding the causative events and mechanisms in the pathogenesis are equally important for translation. Greater efforts are necessary to fill in the gaps and overcome a variety of confounds in the generation, study design, testing, and evaluation of animal models and the application to future novel anti-dementia drug trials. A greater variety of potential disease mechanisms must be entertained to enhance progress.

15 Review Therapeutic potential of mGluR5 targeting in Alzheimer's disease. 2015

Kumar, Anil / Dhull, Dinesh K / Mishra, Pooja S. ·UGC Centre of Advanced Studies, University Institute of Pharmaceutical Sciences, Panjab University Chandigarh, India. · Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences Bangalore, India. ·Front Neurosci · Pubmed #26106290.

ABSTRACT: Decades of research dedicated toward Alzheimer's disease (AD) has culminated in much of the current understanding of the neurodegeneration associated with disease. However, delineating the pathophysiology and finding a possible cure for the disease is still wanting. This is in part due to the lack of knowledge pertaining to the connecting link between neurodegenerative and neuroinflammatory pathways. Consequently, the inefficacy and ill-effects of the drugs currently available for AD encourage the need for alternative and safe therapeutic intervention. In this review we highlight the potential of mGluR5, a metabotropic glutamatergic receptor, in understanding the mechanism underlying the neuronal death and neuroinflammation in AD. We also discuss the role of mGlu5 receptor in mediating the neuron-glia interaction in the disease. Finally, we discuss the potential of mGluR5 as target for treating AD.

16 Review A review on Alzheimer's disease pathophysiology and its management: an update. 2015

Kumar, Anil / Singh, Arti / Ekavali, ?. ·Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh 160014, India. Electronic address: kumaruips@yahoo.com. · Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh 160014, India. ·Pharmacol Rep · Pubmed #25712639.

ABSTRACT: Alzheimer's disease acknowledged as progressive multifarious neurodegenerative disorder, is the leading cause of dementia in late adult life. Pathologically it is characterized by intracellular neurofibrillary tangles and extracellular amyloidal protein deposits contributing to senile plaques. Over the last two decades, advances in the field of pathogenesis have inspired the researchers for the investigation of novel pharmacological therapeutics centered more towards the pathophysiological events of the disease. Currently available treatments i.e. acetylcholinesterase inhibitors (rivastigmine, galantamine, donepezil) and N-methyl d-aspartate receptor antagonist (memantine) contribute minimal impact on the disease and target late aspects of the disease. These drugs decelerate the progression of the disease, provide symptomatic relief but fail to achieve a definite cure. While the neuropathological features of Alzheimer's disease are recognized but the intricacies of the mechanism have not been clearly defined. This lack of understanding regarding the pathogenic process may be the likely reason for the non-availability of effective treatment which can prevent onset and progression of the disease. Owing to the important progress in the field of pathophysiology in the last couple of years, new therapeutic targets are available that should render the underlying disease process to be tackled directly. In this review, authors will discusses the different aspects of pathophysiological mechanisms behind Alzheimer's disease and its management through conventional drug therapy, including modern investigational therapeutic strategies, recently completed and ongoing.

17 Review An overview of various mammalian models to study chronic copper intoxication associated Alzheimer's disease like pathology. 2015

Pal, Amit / Prasad, Rajendra. ·Department of Biochemistry, PGIMER, Chandigarh, 160012, India. ·Biometals · Pubmed #25307560.

ABSTRACT: Chronic copper toxicity has been long known to cause hepatotoxicity and liver cirrhosis as observed in Wilson's disease; however, substantial evidence accrued over the time have shown considerable increase in animal studies demonstrating Alzheimer's disease like pathology due to chronic copper-intoxication under certain conditions. This review integrates the contemporary mammalian studies in which the effect of chronic copper intoxication was assessed on the central nervous system and cognition of animals.

18 Review Towards a unified vision of copper involvement in Alzheimer's disease: a review connecting basic, experimental, and clinical research. 2015

Pal, Amit / Siotto, Mariacristina / Prasad, Rajendra / Squitti, Rosanna. ·Department of Biochemistry, PGIMER, Chandigarh, India. · Don Carlo Gnocchi Foundation ONLUS, Milan, Italy. · Fatebenefratelli Foundation, AFaR Division; Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy Laboratorio di Neurodegenerazione, IRCCS San Raffaele Pisana, Italy. ·J Alzheimers Dis · Pubmed #25261447.

ABSTRACT: Copper is an essential micronutrient for physiological cell functioning and central nervous system (CNS) development. Indeed, it is a cofactor of many proteins and enzymes in a number of molecular pathways, including energy generation, oxygen transportation, hematopoiesis, cellular growth and metabolism, and signal transduction. This is because it serves as a catalyst of reduction-oxidation (redox) reactions in these processes. When copper is kept under control, bound to special proteins, it yields key properties. However, when it spirals out of control, it is exchanged among small compounds (it is loosely bound to them), and its redox activity makes it dangerous for cell viability, promoting oxidative stress. Copper homeostasis in the CNS is securely synchronized, and perturbations in brain copper levels are known to underlie the pathoetiology of wide spectrum of common neurodegenerative disorders, including Alzheimer's disease. The main objective of this review is to provide some of the most relevant evidence gleaned from recent studies conducted on animal models and humans, and to discuss the evidence as it pertains to a new concept: Aberrant copper metabolism, which appears to have a genetic basis, is a modifiable risk factor accelerating Alzheimer's disease and initiation/progression of cognitive deficits in a percentage of susceptible persons.

19 Review Predictive association of copper metabolism proteins with Alzheimer's disease and Parkinson's disease: a preliminary perspective. 2014

Pal, Amit / Kumar, Ashok / Prasad, Rajendra. ·Department of Biochemistry, PGIMER, Chandigarh, 160012, India. ·Biometals · Pubmed #24435851.

ABSTRACT: Neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD), constitute a major worldwide health problem. Several hypothesis have been put forth to elucidate the basis of onset and pathogenesis of AD and PD; however, till date, none of these seems to clearly elucidate the complex pathoetiology of these disorders. Notably, copper dyshomeostasis has been shown to underlie the pathophysiology of several neurodegenerative diseases including AD and PD. Numerous studies have concluded beyond doubt that imbalance in copper homeostatic mechanisms in conjunction with aging causes an acceleration in the copper toxicity elicited oxidative stress, which is detrimental to the central nervous system. Amyloid precursor protein and α-synuclein protein involved in AD and PD are copper binding proteins, respectively. In this review, we have discussed the possible association of copper metabolism proteins with AD and PD along with briefly outlining the expanding proportion of "copper interactome" in human biology. Using network biology, we found that copper metabolism proteins, superoxide dismutase 1 and ceruloplasmin may represent direct and indirect link with AD and PD, respectively.

20 Review Preclinical non-human models to combat dementia. 2013

Banik, Avijit / Anand, Akshay. ·Neuroscience Research Lab, Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, INDIA. ·Ann Neurosci · Pubmed #25206006.

ABSTRACT: Dementia is characterized by a certain degree of memory loss with disabled intellectual functioning, which mostly presents as Alzheimer's disease. The underlying causes range from gene mutations, lifestyle factors, and other environmental influences to brain injuries and normal aging. Although there have been many rodent and non-human primate models created by various drugs, neurotoxins and genetic ablation but the current scenario does not exhibit a well characterized animal model to evaluate novel compounds and various treatment strategies for dementia. Therefore, a comprehensive model exhibiting the pathologies and neuro-behavioral parameters close to this syndrome is very much needed. This report discusses the various experimental strategies to create animal models of dementia.

21 Review Spontaneous and induced nontransgenic animal models of AD: modeling AD using combinatorial approach. 2013

Kaushal, Alka / Wani, Willayat Yousuf / Anand, R / Gill, Kiran Dip. ·Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India. ·Am J Alzheimers Dis Other Demen · Pubmed #23687185.

ABSTRACT: Alzheimer's disease (AD), the most common neurodegenerative and dementing disorder, is characterized by extracellular amyloid deposition, intracellular neurofibrillary tangle formation, and neuronal loss. We are still behind in AD research in terms of knowledge regarding understanding its pathophysiology and designing therapeutics because of the lack of an accurate animal model for AD. A complete animal model of AD should imitate all the cognitive, behavioral, and neuropathological features of the disease. Partial models are currently in use, which only mimic specific and not all of the components of AD pathology. Currently the transgenic animals are the popular models for AD research, but different genetic backgrounds of these transgenic animals remain a major confounding factor. This review attempts to summarize the current literature on nontransgenic animal models of AD and to highlight the potential of exploiting spontaneous and induced animal models for neuropathological, neurochemical, neurobehavioral, and neuroprotective studies of AD.

22 Review Insulin resistance: an emerging link in Alzheimer's disease. 2013

Medhi, Bikash / Chakrabarty, Mrinmoy. ·Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Research Block B, 4th Floor, Room No. 4043, Chandigarh, 160012, India, drbikashus@yahoo.com. ·Neurol Sci · Pubmed #23670236.

ABSTRACT: Relentless progression of Alzheimer's disease (AD) poses a grave situation for the biomedical community to tackle. Agents starting as hot favorites in clinical trials have failed in later stages and it is time we reconsidered our approaches to intervene the disease. Quite some interesting work in the last decade has introduced a new school of thought which factors in neuronal glycemic imbalance as a major component for the development of AD. Insulin resistance in the brain has brought forward subsequent sequelae which might work towards amyloid accretion and/or tau hyperphosphorylation. It is also pointed out that insulin works by distributing iron to neuronal tissue and an insulin resistant state throws it off gear leading to iron overloading of neurons which is ultimately detrimental. A relatively recent investigation finds the role of c-Jun-N-terminal kinase (JNK3) in AD which also seems to bear a link with insulin resistance.

23 Review Drug development status for Alzheimer's disease: present scenario. 2013

Misra, Shubham / Medhi, Bikash. ·Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India. ·Neurol Sci · Pubmed #23392897.

ABSTRACT: Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might ameliorate the disease process. Research in the field of Alzheimer's disease therapy has been partly successful in terms of developing symptomatic treatments, but also had several failures in terms of developing disease-modifying therapies. These successes and failures have led to a debate about the potential deficiencies in our understanding of the pathogenesis of Alzheimer's disease and potential pitfalls in diagnosis, choice of therapeutic targets, development of drug candidates, and design of clinical trials. Many clinical and experimental studies are ongoing, but we need to acknowledge that a single cure for Alzheimer's disease is unlikely to be found and that the approach to drug development for this disorder needs to be reconsidered. Preclinical research is constantly providing us with new information on pieces of the complex Alzheimer's disease puzzle, and an analysis of this information might reveal patterns of pharmacological interactions instead of single potential drug targets. Several promising randomized controlled trials are ongoing, and the increased collaboration between pharmaceutical companies, basic researchers, and clinical researchers has the potential to bring us closer to developing an optimum pharmaceutical approach for the treatment of Alzheimer's disease.

24 Review The animal models of dementia and Alzheimer's disease for pre-clinical testing and clinical translation. 2012

Anand, Akshay / Banik, Avijit / Thakur, Keshav / Masters, Colin L. ·Department of Neurology, Post Graduate institute of Medical Education and Research, Chandigarh, India. akshay1anand@rediffmail.com ·Curr Alzheimer Res · Pubmed #22698073.

ABSTRACT: Dementia is a clinical syndrome with abnormal degree of memory loss and impaired ability to recall events from the past often characterized by Alzheimer's disease. The various strategies to treat dementia need validation of novel compounds in suitable animal models for testing their safety and efficacy. These may include novel anti-amnesic drugs derived from synthetic chemistry or those derived from traditional herbal sources. Multiple approaches have been adopted to create reliable animal models ranging from rodents to non-human primates, where the animals are exposed to a predetermined injury or causing genetic ablation across specific regions of brain suspected to affect learning functions. In this review various animal models for Alzheimer's disease and treatment strategies in development of anti dementia drugs are discussed and an attempt has been made to provide a comprehensive report of the latest developments in the field.

25 Review Road to Alzheimer's disease: the pathomechanism underlying. 2012

Anand, R / Kaushal, Alka / Wani, Willayat Yousuf / Gill, Kiran Dip. ·Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India. ·Pathobiology · Pubmed #22205086.

ABSTRACT: Alzheimer's disease (AD), the most common cause of dementia, results from the interplay of various deregulated mechanisms triggering a complex pathophysiology. The neurons suffer from and slowly succumb to multiple irreversible damages, resulting in cell death and thus memory deficits that characterize AD. In spite of our vast knowledge, it is still unclear as to when the disease process starts and how long the perturbations continue before the disease manifests. Recent studies provide sufficient evidence to prove amyloid β (Aβ) as the primary cause initiating secondary events, but Aβ is also known to be produced under normal conditions and to possess physiological roles, hence, the questions that remain are: What are the factors that lead to abnormal Aβ production? When does Aβ turn into a pathological molecule? What is the chain of events that follows Aβ? The answers are still under debate, and further insight may help us in creating better diagnostic and therapeutic options in AD. The present article attempts to review the current literature regarding AD pathophysiology and proposes a pathophysiologic cascade in AD.

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