TY  - JOUR
AU  - Freisem, Dennis
AU  - Hoenigsperger, Helene
AU  - Catanese, Alberto
AU  - Sparrer, Konstantin
TI  - Inborn errors of canonical autophagy in neurodegenerative diseases.
JO  - Human molecular genetics
VL  - 34
IS  - R1
SN  - 0964-6906
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DZNE-2025-01156
SP  - R23 - R34
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Autophagy: genetics
KW  - Neurodegenerative Diseases: genetics
KW  - Neurodegenerative Diseases: pathology
KW  - Neurodegenerative Diseases: metabolism
KW  - Animals
KW  - Mitophagy: genetics
KW  - Parkinson Disease: genetics
KW  - Parkinson Disease: pathology
KW  - Mutation
KW  - Proteostasis: genetics
KW  - Amyotrophic Lateral Sclerosis: genetics
KW  - Amyotrophic Lateral Sclerosis: pathology
KW  - autophagy (Other)
KW  - innate immunity (Other)
KW  - monogenic diseases (Other)
KW  - neurodegenerative diseases (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40304712
C2  - pmc:PMC12501978
DO  - DOI:10.1093/hmg/ddae179
UR  - https://pub.dzne.de/record/281633
ER  -