Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Alzheimer Disease: HELP
Articles by John S. Lazo
Based on 2 articles published since 2010
(Why 2 articles?)
||||

Between 2010 and 2020, John S. Lazo wrote the following 2 articles about Alzheimer Disease.
 
+ Citations + Abstracts
1 Review Aberrant Neuronal Cell Cycle Re-Entry: The Pathological Confluence of Alzheimer's Disease and Brain Insulin Resistance, and Its Relation to Cancer. 2019

Koseoglu, Mehmet Murat / Norambuena, Andrés / Sharlow, Elizabeth R / Lazo, John S / Bloom, George S. ·Department of Pharmacology, University of Virginia, Charlottesville, VA, USA. · Department of Biology, University of Virginia, Charlottesville, VA, USA. · Department of Chemistry, University of Virginia, Charlottesville, VA, USA. · Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA. · Department of Cell Biology, University of Virginia, Charlottesville, VA, USA. · Department of Neuroscience, University of Virginia, Charlottesville, VA, USA. ·J Alzheimers Dis · Pubmed #30452418.

ABSTRACT: Aberrant neuronal cell cycle re-entry (CCR) is a phenomenon that precedes and may mechanistically lead to a majority of the neuronal loss observed in Alzheimer's disease (AD). Recent developments concerning the regulation of aberrant neuronal CCR in AD suggest that there are potential intracellular signaling "hotspots" in AD, cancer, and brain insulin resistance, the latter of which is characteristically associated with AD. Critically, these common signaling nodes across different human diseases may represent currently untapped therapeutic opportunities for AD. Specifically, repurposing of existing US Food and Drug Administration-approved pharmacological agents, including experimental therapeutics that target the cell cycle in cancer, may be an innovative avenue for future AD-directed drug discovery and development. In this review we discuss overlapping aspects of AD, cancer, and brain insulin resistance from the perspective of neuronal CCR, and consider strategies to exploit them for prevention or therapeutic intervention of AD.

2 Review Reduced brain insulin signaling: A seminal process in Alzheimer's disease pathogenesis. 2018

Bloom, George S / Lazo, John S / Norambuena, Andrés. ·Department of Biology, University of Virginia, Charlottesville, VA, USA; Department of Cell Biology, University of Virginia, Charlottesville, VA, USA; Department of Neuroscience, University of Virginia, Charlottesville, VA, USA. Electronic address: gsb4g@virginia.edu. · Department of Pharmacology, University of Virginia, Charlottesville, VA, USA; Department of Chemistry, University of Virginia, Charlottesville, VA, USA. · Department of Biology, University of Virginia, Charlottesville, VA, USA. ·Neuropharmacology · Pubmed #28965829.

ABSTRACT: The synaptic dysfunction and death of neurons that mediate memory and cognition account together for the behavioral symptoms of Alzheimer's disease (AD). Reduced insulin signaling in the brain is a hallmark of AD patients, even in the absence of systemic type 1 or type 2 diabetes, prompting some researchers to refer to AD as brain-specific, or type 3 diabetes. A key question that arises about this signature feature of AD is "how, if at all, does the brain's impaired ability to utilize insulin contribute to the behavioral deficits associated with AD?" The fact that type 2 diabetes is a risk factor for AD suggests a causative role for impaired insulin responsiveness in AD pathogenesis, but how that might occur at a detailed molecular level had been elusive. Here we review recent findings that mechanistically link soluble forms of amyloid-β (Aβ) and tau, the respective building blocks of the amyloid plaques and neurofibrillary tangles that accumulate in the brains of AD patients, with neuronal decline that is associated with poor insulin responsiveness and may begin long before AD symptoms become evident. We discuss how Aβ and tau work coordinately to deprive neurons of functionally accessible insulin receptors and dysregulate normal signaling by the protein kinase, mTOR. Finally, we suggest how newly gained knowledge about pathogenic signaling caused by reduced brain insulin signaling might be exploited for improved early detection and therapeutic intervention for AD. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'