Autophagy gone awry in neurodegenerative diseases

By Esther Wong, A. Cuervo. Nature Neuroscience, 2010

921 citations recorded by the source corpus.

Autophagy is essential for neuronal homeostasis, and its dysfunction has been directly linked to a growing number of neurodegenerative disorders. The reasons behind autophagic failure in degenerating neurons can be very diverse because of the different steps required for autophagy and the characterization of the molecular players involved in each of them. Understanding the step(s) affected in the autophagic process in each disorder could explain differences in the course of these pathologies and will be essential to developing targeted therapeutic approaches for each disease based on modulation of autophagy. Here we present examples of different types of autophagic dysfunction described in common neurodegenerative disorders and discuss the prospect of exploring some of the recently identified autophagic variants and the interactions among autophagic and non-autophagic proteolytic systems as possible future therapeutic targets.

Subfields: Epidemiology, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/d4466adcbeb73a468822bf8efe70acae87a9290e

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Citations in the corpus

Autophagy‐based unconventional secretory pathway for extracellular delivery of IL‐1β (2011, background): “…and in human health (Mizushima et al, 2008) including aging (Alavez et al, 2011), cancer (Guo et al, 2011), neurodegenera- tion (Renna et al, 2010; Wong and Cuervo, 2010), myopathies (Romanello et al, 2010), metabolic disorders (Gonzalez et al, 2011), infections, immunity, and inflammatory…”
Autophagy Failure in Alzheimer's Disease – Locating the Primary Defect (2011, background): “Strong autophagy induction in associationwith neurodegeneration and autophagic cell death is so far uncommon compared to neurological responses associated with autophagy deficiency (Nixon, 2006; Wong and Cuervo, 2010).”
Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways. (2011, background): “Finally, we and others have recently proposed that lysosomal enhancement could be used as a therapeutic strategy for the treatment of LSDs and neurodegenerative diseases (14,15,79,80).”
Converging mechanisms in ALS and FTD: Disrupted RNA and protein homeostasis (2013, neutral): “Moreover , enthusiasm for the rationale of autophagy induction must be tempered by recognition that simply activating the autophagy pathway may cause cytosolic depletion of essential organelles (reviewed in Wong and Cuervo, 2010), and it should be recognized that autophagy is a double-edged sword.”
Measuring in vivo mitophagy (2015, background): “There ular Cell 60, 685–696, November 19, 2015 ª2015 Elsevier Inc. 693 is particular interest in the role of autophagy and more specifically mitophagy as a contributor to neurodegenerative disease, and to aging itself (Madeo et al., 2015; Rubinsztein et al., 2011; Wong and Cuervo, 2010).”
TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity (2013, methodology): “The transfection into HEK 293 cells was carried out using the calcium-phosphate method, and included the packaging plasmids pDP6 encoding AAV6 capsid proteins (3, 4).”
The cell biology of disease: lysosomal storage disorders: the cellular impact of lysosomal dysfunction. (2012, neutral): “Impairment of autophagy and escalation of cytoplasmic protein aggregation are shared between neurodegenerative LSDs and more common neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, Huntington’s disease, and amyotrophic lateral sclerosis (ALS; García-Arencibia et al., 2010; Wong and Cue”