Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Parkinson Disease: HELP
Articles by Akhilesh Pandey
Based on 3 articles published since 2010
(Why 3 articles?)
||||

Between 2010 and 2020, Akhilesh Pandey wrote the following 3 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Article GBA1 deficiency negatively affects physiological α-synuclein tetramers and related multimers. 2018

Kim, Sangjune / Yun, Seung Pil / Lee, Saebom / Umanah, George Essien / Bandaru, Veera Venkata Ratnam / Yin, Xiling / Rhee, Peter / Karuppagounder, Senthilkumar S / Kwon, Seung-Hwan / Lee, Hojae / Mao, Xiaobo / Kim, Donghoon / Pandey, Akhilesh / Lee, Gabsang / Dawson, Valina L / Dawson, Ted M / Ko, Han Seok. ·Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130. · Mckusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; hko3@jhmi.edu. · Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130. ·Proc Natl Acad Sci U S A · Pubmed #29311330.

ABSTRACT: Accumulating evidence suggests that α-synuclein (α-syn) occurs physiologically as a helically folded tetramer that resists aggregation. However, the mechanisms underlying the regulation of formation of α-syn tetramers are still mostly unknown. Cellular membrane lipids are thought to play an important role in the regulation of α-syn tetramer formation. Since glucocerebrosidase 1 (GBA1) deficiency contributes to the aggregation of α-syn and leads to changes in neuronal glycosphingolipids (GSLs) including gangliosides, we hypothesized that GBA1 deficiency may affect the formation of α-syn tetramers. Here, we show that accumulation of GSLs due to GBA1 deficiency decreases α-syn tetramers and related multimers and increases α-syn monomers in CRISPR-GBA1 knockout (KO) SH-SY5Y cells. Moreover, α-syn tetramers and related multimers are decreased in N370S

2 Article Chromosome-centric human proteome project: deciphering proteins associated with glioma and neurodegenerative disorders on chromosome 12. 2014

Gupta, Manoj Kumar / Jayaram, Savita / Madugundu, Anil K / Chavan, Sandip / Advani, Jayshree / Pandey, Akhilesh / Thongboonkerd, Visith / Sirdeshmukh, Ravi. ·Institute of Bioinformatics, International Tech Park, Bangalore 560066, India. ·J Proteome Res · Pubmed #24804578.

ABSTRACT: In line with the aims of the Chromosome-centric Human Proteome Project (C-HPP) to completely annotate proteins of each chromosome and biology/disease driven HPP (B/D-HPP) to decipher their relation to diseases, we have generated a nonredundant catalogue of protein-coding genes for Chromosome 12 (Chr. 12) and further annotated proteins associated with major neurological disorders. Integrating high level proteomic evidence from four major databases (neXtProt, Global Proteome Machine (GPMdb), PeptideAtlas, and Human Protein Atlas (HPA)) along with Ensembl data resource resulted in the identification of 1066 protein coding genes, of which 171 were defined as "missing proteins" based on the weak or complete absence of experimental evidence. With functional annotations using DAVID and GAD, about 40% of the proteins could be grouped as brain related with implications in cancer or neurological disorders. We used published and unpublished high confidence mass spectrometry data from our group and other literature consisting of more than 5000 proteins derived from clinical specimens from patients with human gliomas, Alzheimer's disease, and Parkinson's disease and mapped it onto Chr. 12. We observed a total of 202 proteins mapping to human Chr. 12, 136 of which were differentially expressed in these disease conditions as compared to the normal. Functional grouping indicated their association with cell cycle, cell-to-cell signaling, and other important processes and networks, whereas their disease association analysis confirmed neurological diseases and cancer as the major group along with psycological disorders, with several overexpressed genes/proteins mapping to 12q13-15 amplicon region. Using multiple strategies and bioinformatics tools, we identified 103 differentially expressed proteins to have secretory potential, 17 of which have already been reported in direct analysis of the plasma or cerebrospinal fluid (CSF) from the patients and 21 of them mapped to cancer associated protein (CAPs) database that are amenable to selective reaction monitoring (SRM) assays for targeted proteomic analysis. Our analysis also reveals, for the first time, mass spectrometric evidence for two "missing proteins" from Chr. 12, namely, synaptic vesicle 2-related protein (SVOP) and IQ motif containing D (IQCD). The analysis provides a snapshot of Chr. 12 encoded proteins associated with gliomas and major neurological conditions and their secretability which can be used to drive efforts for clinical applications.

3 Article Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease. 2014

Martin, Ian / Kim, Jungwoo Wren / Lee, Byoung Dae / Kang, Ho Chul / Xu, Jin-Chong / Jia, Hao / Stankowski, Jeannette / Kim, Min-Sik / Zhong, Jun / Kumar, Manoj / Andrabi, Shaida A / Xiong, Yulan / Dickson, Dennis W / Wszolek, Zbigniew K / Pandey, Akhilesh / Dawson, Ted M / Dawson, Valina L. ·Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Age-Related and Brain Disease Research Center, Department of Neuroscience, Kyung Hee University, Seoul 130-701, South Korea. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Ajou University School of Medicine, Suwon 443-749, South Korea. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA. · Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA. · Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA; Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130, USA. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA. Electronic address: tdawson@jhmi.edu. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130, USA. Electronic address: vdawson@jhmi.edu. ·Cell · Pubmed #24725412.

ABSTRACT: Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of familial and sporadic Parkinson's disease (PD). Elevated LRRK2 kinase activity and neurodegeneration are linked, but the phosphosubstrate that connects LRRK2 kinase activity to neurodegeneration is not known. Here, we show that ribosomal protein s15 is a key pathogenic LRRK2 substrate in Drosophila and human neuron PD models. Phosphodeficient s15 carrying a threonine 136 to alanine substitution rescues dopamine neuron degeneration and age-related locomotor deficits in G2019S LRRK2 transgenic Drosophila and substantially reduces G2019S LRRK2-mediated neurite loss and cell death in human dopamine and cortical neurons. Remarkably, pathogenic LRRK2 stimulates both cap-dependent and cap-independent mRNA translation and induces a bulk increase in protein synthesis in Drosophila, which can be prevented by phosphodeficient T136A s15. These results reveal a novel mechanism of PD pathogenesis linked to elevated LRRK2 kinase activity and aberrant protein synthesis in vivo.