The Role of α-Synuclein in the Regulation of Serotonin System: Physiological and Pathological Features.
Parkinson’s disease
depression
raphe nuclei
serotonin
α-synuclein
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
13 Feb 2023
13 Feb 2023
Historique:
received:
20
12
2022
revised:
30
01
2023
accepted:
09
02
2023
entrez:
25
2
2023
pubmed:
26
2
2023
medline:
26
2
2023
Statut:
epublish
Résumé
In patients affected by Parkinson's disease (PD), up to 50% of them experience cognitive changes, and psychiatric disturbances, such as anxiety and depression, often precede the onset of motor symptoms and have a negative impact on their quality of life. Pathologically, PD is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and the presence of intracellular inclusions, called Lewy bodies and Lewy neurites, composed mostly of α-synuclein (α-Syn). Much of PD research has focused on the role of α-Syn aggregates in the degeneration of SNc DA neurons due to the impact of striatal DA deficits on classical motor phenotypes. However, abundant Lewy pathology is also found in other brain regions including the midbrain raphe nuclei, which may contribute to non-motor symptoms. Indeed, dysfunction of the serotonergic (5-HT) system, which regulates mood and emotional pathways, occurs during the premotor phase of PD. However, little is known about the functional consequences of α-Syn inclusions in this neuronal population other than DA neurons. Here, we provide an overview of the current knowledge of α-Syn and its role in regulating the 5-HT function in health and disease. Understanding the relative contributions to α-Syn-linked alterations in the 5-HT system may provide a basis for identifying PD patients at risk for developing depression and could lead to a more targeted therapeutic approach.
Identifiants
pubmed: 36831077
pii: biomedicines11020541
doi: 10.3390/biomedicines11020541
pmc: PMC9953742
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : Spanish Ministry of Economy and Competitiveness
ID : PID2019-105136RB-100
Organisme : Center for Networked Biomedical Research on Mental Health (CIBERSAM)
ID : CB/07/09/0034 and CB/07/09/0008
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