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Table 3 Autophagy in common chronic neurodegenerative diseases.

From: All-you-can-eat: autophagy in neurodegeneration and neuroprotection

Disease Autophagosomal phenotype Ref.
Alzheimer disease Autophagy appears impaired, autophagosomes accumulate, endosomal-lysosomal abnormalities, increased mitophagy, reduction of macroautophagy enhances pathology, pharmacological activation of macroautophagy can promote the clearance of Aβ/APP and reduces tau pathology, autophagosomes contain APP/Aβ/secretases. [206, 208, 59, 62, 204, 207, 203, 209, 205, 57, 58, 118]
Parkinson disease Autophagy/mitophagy appears impaired, autophagosome-like structures accumulate, pharmacological activation of macroautophagy enhances α-synuclein clearance and is neuroprotective, α-synuclein is a target of CMA and macroautophagy and the proteasome, dopamine-modified/mutated α-synuclein blocks CMA and dopamine induces autophagic cell death and α-synuclein accumulation, mutant UCH-L1 binds to LAMP2A and inhibits CMA. [220, 214, 215, 213, 219, 212, 102, 216, 192, 210, 211, 218, 217, 117]
Huntington diseases Impaired sorting/degradation of autophagosomes, autophagosomes accumulate, BECN1 is recruited to htt inclusions and BECN1 reduction causes enhanced htt accumulation, pharmacological or signaling mediated activation of macroautophagy reduces htt toxicity, mTOR is sequestered into htt inclusions, which causes macroautophagy activation. [225, 227, 228, 216, 229231, 203, 221, 226, 224, 195, 223, 222]
Frontotemporal dementia Impaired endosome maturation, enlarged autophagosome accumulation, mutant CHMP2B disturbs the ESCRT-III complex for endosomal sorting which results in polyU/SQSTM1 aggregates. [162, 85]
Amyotrophic lateral sclerosis Impaired early endosomes, impaired sorting/degradation of autophagosomes, CHMP2B disturbs the ESCRT-III complex for endosomal/MVB sorting which results in polyU/SQSTM1 aggregates, MVBs are required for TDP-43 clearance, Lithium activates protective autophagy. [232, 86, 162, 233]