Endosomal Acid-Base Homeostasis in Neurodegenerative Diseases.
Alzheimer’s disease
Amyloid
ApoE4
Endosomal pH
NHE6
Na+/H+ exchanger
Journal
Reviews of physiology, biochemistry and pharmacology
ISSN: 0303-4240
Titre abrégé: Rev Physiol Biochem Pharmacol
Pays: Germany
ID NLM: 0434624
Informations de publication
Date de publication:
2023
2023
Historique:
pubmed:
2
8
2020
medline:
1
2
2023
entrez:
2
8
2020
Statut:
ppublish
Résumé
Neurodegenerative disorders are debilitating and largely untreatable conditions that pose a significant burden to affected individuals and caregivers. Overwhelming evidence supports a crucial preclinical role for endosomal dysfunction as an upstream pathogenic hub and driver in Alzheimer's disease (AD) and related neurodegenerative disorders. We present recent advances on the role of endosomal acid-base homeostasis in neurodegeneration and discuss evidence for converging mechanisms. The strongest genetic risk factor in sporadic AD is the ε4 allele of Apolipoprotein E (ApoE4), which potentiates pre-symptomatic endosomal dysfunction and prominent amyloid beta (Aβ) pathology, although how these pathways are linked mechanistically has remained unclear. There is emerging evidence that the Christianson syndrome protein NHE6 is a prominent ApoE4 effector linking endosomal function to Aβ pathologies. By functioning as a dominant leak pathway for protons, the Na
Identifiants
pubmed: 32737755
doi: 10.1007/112_2020_25
pmc: PMC7614123
mid: EMS130379
doi:
Substances chimiques
Amyloid beta-Peptides
0
Apolipoprotein E4
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
195-231Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : DBT-Wellcome Trust India Alliance
ID : IA/E/17/1/503665
Pays : India
Organisme : NIDDK NIH HHS
ID : R01 DK108304
Pays : United States
Informations de copyright
© 2020. The Author(s), under exclusive license to Springer Nature Switzerland AG.
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