Autophagy Induction as a Therapeutic Strategy for Neurodegenerative Diseases

Abstract

 Autophagy delivers cytoplasmic cargoes to lysosomes for degradation  It degrades many aggregate-prone proteins responsible for neurodegenerative disease  Enhancing autophagy has therapeutic potential in common neurodegenerative diseases  Evidence in cells and in vivo demonstrates promising results in many disease models  Outcomes may depend on how autophagy impacts disease pathogenesis

The Dynamic Proteome of Oligodendrocyte Lineage Differentiation Features Planar Cell Polarity and Macroautophagy Pathways

“…Therefore, the induced autophagy would promote these cells' function in clearing cellular and myelin debris, protein aggresomes, and their development toward achieving remyelination [ 64 , 70 , 71 ]. Currently, the pharmaceutical compounds that are used to induce autophagy may target signalling pathways other than autophagy [ 72 ]. One potential strategy to minimize adverse effects is to identify more specific autophagy regulators and mechanisms in every cell type to help to achieve targeted autophagy modulations [ 72 , 73 ].…”

“…Currently, the pharmaceutical compounds that are used to induce autophagy may target signalling pathways other than autophagy [ 72 ]. One potential strategy to minimize adverse effects is to identify more specific autophagy regulators and mechanisms in every cell type to help to achieve targeted autophagy modulations [ 72 , 73 ].…”

The neuroprotective effects of α7 nicotinic acetylcholine receptor against mutant copper-zinc superoxide dismutase 1-mediated toxicity

“…Autophagy dysfunction has been implicated in various neurodegenerative diseases, including ALS [45,46]. The notion that autophagy dysfunction contributes to ALS pathogenesis is strongly supported by the identi cation of numerous genes associated with familial ALS also involved in regulation of autophagy, including SQSTM1 [47], OPTN [4], TBK1 [48], and VCP [49].…”

“…There are two major pathways for cellular protein degradation: the ubiquitin proteasome system (UPS), and autophagy. Autophagy has been shown to degrade both soluble and aggregated protein substrates that are too large to pass through the pore of the proteasome, such as the toxic SOD1 protein aggregates, while UPS primarily degrades soluble SOD1, suggesting that autophagy regulation is critical for improving ALS pathology [46,50].…”

“…Conversely, abnormalities (activations) in autophagy have been observed in numerous neurodegenerative diseases, including ALS [56]. Pharmacological and genetic modulation of autophagy may result in diverse and even detrimental outcomes to the survival of ALS models; interventions targeting genes including mSOD1, FUS and TDP-43 [46,50] have shown that it may be necessary to jointly consider the speci c effects of each individual mutation, pathology, and possibly other context-dependent in uences. These results suggest the need for developing autophagy inducers with higher speci city and lower cytotoxicity based on ALS pathology [50].…”