Regulation of the proteostasis network by the neuronal system

The protein homeostasis (proteostasis) network is a nexus of molecular mechanisms that act in concert to maintain the integrity of the proteome and ensure proper cellular and organismal functionality. Early in life the proteostasis network efficiently preserves the functionality of the proteome, how...

Full description

Bibliographic Details
Main Authors: Huadong Zhu, Ehud Cohen
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-11-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2023.1290118/full
_version_ 1827773736589197312
author Huadong Zhu
Ehud Cohen
author_facet Huadong Zhu
Ehud Cohen
author_sort Huadong Zhu
collection DOAJ
description The protein homeostasis (proteostasis) network is a nexus of molecular mechanisms that act in concert to maintain the integrity of the proteome and ensure proper cellular and organismal functionality. Early in life the proteostasis network efficiently preserves the functionality of the proteome, however, as the organism ages, or due to mutations or environmental insults, subsets of inherently unstable proteins misfold and form insoluble aggregates that accrue within the cell. These aberrant protein aggregates jeopardize cellular viability and, in some cases, underlie the development of devastating illnesses. Hence, the accumulation of protein aggregates activates different nodes of the proteostasis network that refold aberrantly folded polypeptides, or direct them for degradation. The proteostasis network apparently functions within the cell, however, a myriad of studies indicate that this nexus of mechanisms is regulated at the organismal level by signaling pathways. It was also discovered that the proteostasis network differentially responds to dissimilar proteotoxic insults by tailoring its response according to the specific challenge that cells encounter. In this mini-review, we delineate the proteostasis-regulating neuronal mechanisms, describe the indications that the proteostasis network differentially responds to distinct proteotoxic challenges, and highlight possible future clinical prospects of these insights.
first_indexed 2024-03-11T13:28:02Z
format Article
id doaj.art-ff0e786f8ddf4ebabe9f5fbb766a3149
institution Directory Open Access Journal
issn 2296-889X
language English
last_indexed 2024-03-11T13:28:02Z
publishDate 2023-11-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Molecular Biosciences
spelling doaj.art-ff0e786f8ddf4ebabe9f5fbb766a31492023-11-03T05:53:52ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-11-011010.3389/fmolb.2023.12901181290118Regulation of the proteostasis network by the neuronal systemHuadong ZhuEhud CohenThe protein homeostasis (proteostasis) network is a nexus of molecular mechanisms that act in concert to maintain the integrity of the proteome and ensure proper cellular and organismal functionality. Early in life the proteostasis network efficiently preserves the functionality of the proteome, however, as the organism ages, or due to mutations or environmental insults, subsets of inherently unstable proteins misfold and form insoluble aggregates that accrue within the cell. These aberrant protein aggregates jeopardize cellular viability and, in some cases, underlie the development of devastating illnesses. Hence, the accumulation of protein aggregates activates different nodes of the proteostasis network that refold aberrantly folded polypeptides, or direct them for degradation. The proteostasis network apparently functions within the cell, however, a myriad of studies indicate that this nexus of mechanisms is regulated at the organismal level by signaling pathways. It was also discovered that the proteostasis network differentially responds to dissimilar proteotoxic insults by tailoring its response according to the specific challenge that cells encounter. In this mini-review, we delineate the proteostasis-regulating neuronal mechanisms, describe the indications that the proteostasis network differentially responds to distinct proteotoxic challenges, and highlight possible future clinical prospects of these insights.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1290118/fullproteotoxicityproteostasisneurodegenerationneuropeptidesC. elegansAlzheimer’s disease
spellingShingle Huadong Zhu
Ehud Cohen
Regulation of the proteostasis network by the neuronal system
Frontiers in Molecular Biosciences
proteotoxicity
proteostasis
neurodegeneration
neuropeptides
C. elegans
Alzheimer’s disease
title Regulation of the proteostasis network by the neuronal system
title_full Regulation of the proteostasis network by the neuronal system
title_fullStr Regulation of the proteostasis network by the neuronal system
title_full_unstemmed Regulation of the proteostasis network by the neuronal system
title_short Regulation of the proteostasis network by the neuronal system
title_sort regulation of the proteostasis network by the neuronal system
topic proteotoxicity
proteostasis
neurodegeneration
neuropeptides
C. elegans
Alzheimer’s disease
url https://www.frontiersin.org/articles/10.3389/fmolb.2023.1290118/full
work_keys_str_mv AT huadongzhu regulationoftheproteostasisnetworkbytheneuronalsystem
AT ehudcohen regulationoftheproteostasisnetworkbytheneuronalsystem