AAA+ Protein-Based Technologies to Counter Neurodegenerative Disease.
Journal
Biophysical journal
ISSN: 1542-0086
Titre abrégé: Biophys J
Pays: United States
ID NLM: 0370626
Informations de publication
Date de publication:
23 04 2019
23 04 2019
Historique:
received:
24
01
2019
revised:
21
02
2019
accepted:
13
03
2019
pubmed:
7
4
2019
medline:
4
3
2020
entrez:
7
4
2019
Statut:
ppublish
Résumé
Protein misfolding and overloaded proteostasis networks underlie a range of neurodegenerative diseases. No cures exist for these diseases, but developing effective therapeutic agents targeting the toxic, misfolded protein species in disease is one promising strategy. AAA+ (ATPases associated with diverse cellular activities) protein translocases, which naturally unfold and translocate substrate proteins, could be potent therapeutic agents to disassemble toxic protein conformers in neurodegenerative disease. Here, we discuss repurposing AAA+ protein translocases Hsp104 and proteasome-activating nucleotidase (PAN) to alleviate the toxicity from protein misfolding in neurodegenerative disease. Hsp104 effectively protects various animal models from neurodegeneration underpinned by protein misfolding, and enhanced Hsp104 variants strongly counter neurodegenerative disease-associated protein misfolding toxicity in yeast, Caenorhabditis elegans, and mammalian cells. Similarly, a recently engineered PAN variant (PAN
Identifiants
pubmed: 30952364
pii: S0006-3495(19)30193-6
doi: 10.1016/j.bpj.2019.03.007
pmc: PMC6486517
pii:
doi:
Substances chimiques
Heat-Shock Proteins
0
alpha-Synuclein
0
Adenosine Triphosphatases
EC 3.6.1.-
PAN enzyme
EC 3.6.4.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1380-1385Subventions
Organisme : NINDS NIH HHS
ID : F31 NS101807
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM099836
Pays : United States
Informations de copyright
Copyright © 2019 Biophysical Society. Published by Elsevier Inc. All rights reserved.
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