Autophagy, amyloidogenesis and Alzheimer disease

By Ralph A. Nixon. Journal of Cell Science, 2007

744 citations recorded by the source corpus.

Autophagy is the sole pathway for organelle turnover in cells and is a vital pathway for degrading normal and aggregated proteins, particularly under stress or injury conditions. Recent evidence has shown that the amyloid β peptide is generated from amyloid β precursor protein (APP) during autophagic turnover of APP-rich organelles supplied by both autophagy and endocytosis. Aβ generated during normal autophagy is subsequently degraded by lysosomes. Within neurons, autophagosomes and endosomes actively form in synapses and along neuritic processes but efficient clearance of these compartments requires their retrograde transport towards the neuronal cell body, where lysosomes are most concentrated. In Alzheimer disease, the maturation of autophagolysosomes and their retrograde transport are impeded, which leads to a massive accumulation of `autophagy intermediates' (autophagic vacuoles) within large swellings along dystrophic and degenerating neurites. The combination of increased autophagy induction and defective clearance of Aβ-generating autophagic vacuoles creates conditions favorable for Aβ accumulation in Alzheimer disease.

Subfields: Epidemiology, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/724bf8b1c4a2689f58e498f50d7d8450bba72070

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In Epidemiology

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Citations in the corpus

• Autophagy Failure in Alzheimer's Disease – Locating the Primary Defect (2011, neutral): “1) (Nixon, 2007; Yu et al., 2010).”
• Microautophagy: lesser-known self-eating (2011, neutral): “, Alzheimer disease [71], Creutzfeldt–Jakob disease [72], Gerstmann–Straussler–Scheinker (GSS) [73], and Huntington’s disease [74]), albinism (e.”
• Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. (2011, background): “This leads to an increased accumulation of material in autophagic vacuoles, which is a sign of disturbance in the lysosomal system (271).”
• Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer's Disease (2010, background): “The role of autophagy in AD, however, is not clear[19,27].”