Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases.
10.1007/s12264-023-01115-9
- Author:
Chenjun HU
1
;
Yiqun YAN
1
;
Yanhong JIN
1
;
Jun YANG
2
;
Yongmei XI
3
;
Zhen ZHONG
4
Author Information
1. Department of Neurology of the Second Affiliated Hospital and Department of Human Anatomy, Histology and Embryology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
2. Department of Physiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
3. Division of Human Reproduction and Developmental Genetics, Women's Hospital and Institute of Genetics, Zhejiang University School of Medicine, Hangzhou, 310006, China. xyyongm@zju.edu.cn.
4. Department of Neurology of the Second Affiliated Hospital and Department of Human Anatomy, Histology and Embryology, Zhejiang University School of Medicine, Hangzhou, 310058, China. zhenzhong@zju.edu.cn.
- Publication Type:Review
- Keywords:
Degradation;
Endocytosis;
Endolyosomal leaking;
Neurodegenerative diseases;
Prion-like propagation;
Seeding
- MeSH:
Humans;
Prions;
Neurodegenerative Diseases/pathology*;
Amyloid beta-Peptides;
Alzheimer Disease;
alpha-Synuclein;
tau Proteins;
Parkinson Disease
- From:
Neuroscience Bulletin
2024;40(2):241-254
- CountryChina
- Language:English
-
Abstract:
The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease, or Amyotrophic Lateral Sclerosis. In a process known as 'seeding', prion-like proteins such as amyloid beta, microtubule-associated protein tau, α-synuclein, silence superoxide dismutase 1, or transactive response DNA-binding protein 43 kDa, propagate their misfolded conformations by transforming their respective soluble monomers into fibrils. Cellular and molecular evidence of prion-like propagation in NDs, the clinical relevance of their 'seeding' capacities, and their levels of contribution towards disease progression have been intensively studied over recent years. This review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization, endo-lysosomal leaking, aggregate degradation, and secretion. Debates on the importance of the role of prion-like protein aggregates in NDs, whether causal or consequent, are also discussed. Applications lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.
