Journal Article (Review Article)

DZNE-2025-01156

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Inborn errors of canonical autophagy in neurodegenerative diseases.

Freisem, D.Extern* ; Hoenigsperger, H.Extern* ; Catanese, A.DZNE* ; Sparrer, K.Extern*

2025
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/hmg/ddae179

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.

Keyword(s): Humans (MeSH) ; Autophagy: genetics (MeSH) ; Neurodegenerative Diseases: genetics (MeSH) ; Neurodegenerative Diseases: pathology (MeSH) ; Neurodegenerative Diseases: metabolism (MeSH) ; Animals (MeSH) ; Mitophagy: genetics (MeSH) ; Parkinson Disease: genetics (MeSH) ; Parkinson Disease: pathology (MeSH) ; Mutation (MeSH) ; Proteostasis: genetics (MeSH) ; Amyotrophic Lateral Sclerosis: genetics (MeSH) ; Amyotrophic Lateral Sclerosis: pathology (MeSH) ; autophagy ; innate immunity ; monogenic diseases ; neurodegenerative diseases

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Contributing Institute(s):

1. Translational Protein Biochemistry (AG Böckers)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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