Journal Article (Review Article)

DZNE-2026-00570

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Sphingolipidoses: expanding the spectrum of α-synucleinopathies.

Erskine, D. ; Bronowska, A. K. ; Outeiro, T. F.DZNE* ; Attems, J.

2026
Springer Wien [u.a.]

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Please use a persistent id in citations: doi:10.1007/s00702-025-02925-z

Abstract: Although α-synuclein pathology is typically associated with Lewy body diseases and multiple systems atrophy, increasing evidence indicates that it also occurs in a group of lysosomal storage disorders termed sphingolipidoses caused by the incomplete degradation, and subsequent accumulation, of a class of lipids termed sphingolipids. Notably, a number of genes that cause sphingolipidoses are also risk genes for Lewy body diseases, suggesting aetiological links between these distinct disorders. In the present review, we discuss the sphingolipidoses in which α-synuclein pathology has been reported: Gaucher disease, Krabbe disease, metachromatic leukodystrophy, Tay-Sachs disease and Anderson-Fabry disease, and describe the characteristic clinical and pathological features of these disorders, in addition to the evidence suggesting α-synuclein pathology occurs in these disorders. Finally, we evaluate the pathological mechanisms that underlie these rare disorders, with particular attention to how the enzymatic deficiency, substrate accumulation, or both, could contribute to the genesis of α-synuclein pathology and the implications of this for Lewy body diseases.

Keyword(s): Humans (MeSH) ; Synucleinopathies: pathology (MeSH) ; Synucleinopathies: genetics (MeSH) ; Synucleinopathies: metabolism (MeSH) ; alpha-Synuclein: metabolism (MeSH) ; Sphingolipidoses: pathology (MeSH) ; Sphingolipidoses: genetics (MeSH) ; Sphingolipidoses: metabolism (MeSH) ; Sphingolipidoses: complications (MeSH) ; Animals (MeSH) ; Alpha-synuclein ; Lewy ; Lysosomal storage disorder ; Neurodegeneration ; Parkinson’s ; Sphingolipid ; alpha-Synuclein

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Contributing Institute(s):

1. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)

Research Program(s):

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

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

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