Protein recycling pathways in neurodegenerative diseases

Faisal Fecto, Y Taylan Esengul, Teepu Siddique, Faisal Fecto, Y Taylan Esengul, Teepu Siddique

Abstract

Many progressive neurodegenerative diseases, including Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, and frontotemporal lobe dementia, are associated with the formation of insoluble intracellular proteinaceous inclusions. It is therefore imperative to understand the factors that regulate normal, as well as abnormal, protein recycling in neurons. Dysfunction of the ubiquitin-proteasome or autophagy pathways might contribute to the pathology of various neurodegenerative diseases. Induction of these pathways may offer a rational therapeutic strategy for a number of these diseases.

Figures

Figure 1
Figure 1
Defects in protein recycling pathways in various neurodegenerative diseases. For autophagy, the defect can be at the level of autophagy induction, cargo recognition, autophagosome/lysosome fusion, or lysosomal degradation. AD, Alzheimer disease; ALS, amyotrophic lateral sclerosis; CMA, chaperone-mediated autophagy; FTD, frontotemporal lobe dementia; HD, Huntington disease; mTOR, mammalian target of rapamycin; PD, Parkinson disease; ULK-1, Unc-51 like autophagy activating kinase 1; UPS, ubiquitin-proteasome system.

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