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@ARTICLE{Freisem:281633,
author = {Freisem, Dennis and Hoenigsperger, Helene and Catanese,
Alberto and Sparrer, Konstantin},
title = {{I}nborn errors of canonical autophagy in neurodegenerative
diseases.},
journal = {Human molecular genetics},
volume = {34},
number = {R1},
issn = {0964-6906},
address = {Oxford},
publisher = {Oxford Univ. Press},
reportid = {DZNE-2025-01156},
pages = {R23 - R34},
year = {2025},
abstract = {Neurodegenerative disorders (NDDs), characterized by a
progressive loss of neurons and cognitive function, are a
severe burden to human health and mental fitness worldwide.
A hallmark of NDDs such as Alzheimer's disease, Huntington's
disease, Parkinson's disease (PD), amyotrophic lateral
sclerosis (ALS) and prion diseases is disturbed cellular
proteostasis, resulting in pathogenic deposition of
aggregated protein species. Autophagy is a major cellular
process maintaining proteostasis and integral to innate
immune defenses that mediates lysosomal protein turnover.
Defects in autophagy are thus frequently associated with
NDDs. In this review, we discuss the interplay between NDDs
associated proteins and autophagy and provide an overview
over recent discoveries in inborn errors in canonical
autophagy proteins that are associated with NDDs. While
mutations in autophagy receptors seems to be associated
mainly with the development of ALS, errors in mitophagy are
mainly found to promote PD. Finally, we argue whether
autophagy may impact progress and onset of the disease, as
well as the potential of targeting autophagy as a
therapeutic approach. Concludingly, understanding disorders
due to inborn errors in autophagy-'autophagopathies'-will
help to unravel underlying NDD pathomechanisms and provide
unique insights into the neuroprotective role of autophagy,
thus potentially paving the way for novel therapeutic
interventions.},
subtyp = {Review Article},
keywords = {Humans / Autophagy: genetics / Neurodegenerative Diseases:
genetics / Neurodegenerative Diseases: pathology /
Neurodegenerative Diseases: metabolism / Animals /
Mitophagy: genetics / Parkinson Disease: genetics /
Parkinson Disease: pathology / Mutation / Proteostasis:
genetics / Amyotrophic Lateral Sclerosis: genetics /
Amyotrophic Lateral Sclerosis: pathology / autophagy (Other)
/ innate immunity (Other) / monogenic diseases (Other) /
neurodegenerative diseases (Other)},
cin = {AG Böckers},
ddc = {570},
cid = {I:(DE-2719)1910002},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40304712},
pmc = {pmc:PMC12501978},
doi = {10.1093/hmg/ddae179},
url = {https://pub.dzne.de/record/281633},
}