Medical Science

The Role of Global and Cellular Stress in Neurodegenerative Diseases
Huaxi Xu, Center for Neuroscience and Aging, Burnham Institute for Medical Research

Global and cellular stresses are known to play a key role in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD), Huntington’s disease, Parkinson’s disease, and prion diseases which are characterized by the accumulation of aggregated misfolded proteins. Chronic stress triggers a series of cellular responses such as activation of a molecular chaperone system within the cell, leading to alterations in protein folding, intracellular trafficking, and synaptic activity and memory/cognitive functions. AD, as one of the most common forms of neurodegenerative disorders, is cytopathologically characterized by amyloid plaques consisting of aggregated β-amyloid (Aβ) peptides, and intraneuronal neurofibrillary tangles (NFT) consisting of hyperphosphorylated tau protein in susceptible brain regions, as well as loss of synapses/neurons and hence impaired memory and cognition. Overproduction and aberrant folding of Aβ and hyperphosphorylated tau protein compromises neuronal functions and eventually exterminates neurons. In this session, we will discuss: (1) protein folding stress within the endoplasmic reticulum (ER) where membrane and secretory proteins (namely Aβ and its precursor protein APP) are folded and processed, (2) roles of molecular chaperones in tau protein phosphorylation, aggregation and NFT-associated memory impairments, and (3) the effects of stressful experiences on synapses, cells and microcircuits in the hippocampus and amygdala, in the context of memory and emotional symptoms observed in stress-related psychiatric disorders. Deciphering the role of the stress experience and related molecular pathways/mechanisms in the nervous system is a key to our understanding of pathogenesis of neurodegenerative diseases and developing rational therapeutic strategies against disorders with protein misfolding characteristics.

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Medical Science

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  • Prügivedu

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