Aberrant accumulation of α-synuclein might be linked with the progressive motor deficits in a mouse model of Angelman syndrome
- 1Indian Institute of Technology Kharagpur
Abstract
Dysfunction of maternal UBE3A leads to Angelman syndrome (AS), which is characterized by significant intellectual and motor debilities. However, the molecular underpinnings of the behavioral deficits associated with UBE3A dysfunction remain obscure. In this study, we utilized a model mouse of AS and report, for the first time, that the aberrant accumulation of -synuclein may be linked to the development of AS. Firstly, we demonstrated a progressive deterioration of various motor functions in AS mice beginning from the early adolescent phase. Subsequently, we observed an age-dependent increase in the accumulation of both soluble and insoluble -synuclein, including its pathological variant (pSer129), in the striatum and substantia nigra dopaminergic neurons of AS mice. We also found that Ube3a interacts with -synuclein and promotes its proteasome-mediated degradation, as evidenced by decreased levels of K48-linked polyubiquitinated -synuclein in the brain samples of AS mice in comparison to wild-type animals. Finally, using an RT2 Profiler PCR Array that analysed 84 genes specifically related to dopamine and serotonin pathways, we identified altered transcript level of various genes in the striatal tissues of AS mice that are commonly associated with nigrostriatal dysfunctions in Parkinson's disease. These findings highlight -synuclein as a novel target of Ube3a and suggest that -synuclein pathology may contribute to the progressive motor and other behavioral abnormalities witnessed in AS mice.
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BibTeX
@misc{das2026aberrant,
title = {{Aberrant accumulation of α-synuclein might be linked with the progressive motor deficits in a mouse model of Angelman syndrome}},
author = {S. Das and B. Giri and N. R. Jana},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.27.747679},
url = {https://www.biorxiv.org/content/10.64898/2026.08.27.747679v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Aberrant accumulation of α-synuclein might be linked with the progressive motor deficits in a mouse model of Angelman syndrome
AU - S. Das
AU - B. Giri
AU - N. R. Jana
PY - 2026
DA - 2026/08/27
PB - bioRxiv
DO - 10.64898/2026.08.27.747679
UR - https://www.biorxiv.org/content/10.64898/2026.08.27.747679v1
AB - Dysfunction of maternal UBE3A leads to Angelman syndrome (AS), which is characterized by significant intellectual and motor debilities. However, the molecular underpinnings of the behavioral deficits associated with UBE3A dysfunction remain obscure. In this study, we utilized a model mouse of AS and report, for the first time, that the aberrant accumulation of -synuclein may be linked to the development of AS. Firstly, we demonstrated a progressive deterioration of various motor functions in AS mice beginning from the early adolescent phase. Subsequently, we observed an age-dependent increase in the accumulation of both soluble and insoluble -synuclein, including its pathological variant (pSer129), in the striatum and substantia nigra dopaminergic neurons of AS mice. We also found that Ube3a interacts with -synuclein and promotes its proteasome-mediated degradation, as evidenced by decreased levels of K48-linked polyubiquitinated -synuclein in the brain samples of AS mice in comparison to wild-type animals. Finally, using an RT2 Profiler PCR Array that analysed 84 genes specifically related to dopamine and serotonin pathways, we identified altered transcript level of various genes in the striatal tissues of AS mice that are commonly associated with nigrostriatal dysfunctions in Parkinson's disease. These findings highlight -synuclein as a novel target of Ube3a and suggest that -synuclein pathology may contribute to the progressive motor and other behavioral abnormalities witnessed in AS mice.
ER -