title: Neuronal aggregates: formation, clearance, and spreading.
abstract: Proteostasis is maintained by multiple cellular pathways, including protein synthesis, quality control, and degradation. An imbalance of neuronal proteostasis, associated with protein misfolding and aggregation, leads to proteinopathies or neurodegeneration. While genetic variations and protein modifications contribute to aggregate formation, components of the proteostasis network dictate the fate of protein aggregates. Here we provide an overview of proteostasis pathways and their interplay (particularly autophagy) with the metabolism of disease-related proteins. We review recent studies on neuronal activity-mediated regulation of proteostasis and transcellular propagation of protein aggregates in the nervous system. Targeting proteostasis pathways therapeutically remains an attractive but challenging task.
authors.affiliation: Department of Neurology, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Lim
authors.affiliation: Department of Neurology, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: zhenyu.yue@mssm.edu.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yue
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D066263:Protein Aggregation, Pathological / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D046988:Proteasome Endopeptidase Complex