Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases
Chenjun Hu1 · Yiqun Yan1 · Yanhong Jin1 · Jun Yang2 · Yongmei Xi3 · Zhen Zhong11 Department of Neurology of the Second Afliated 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 Afliated 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
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.
Keywords
Neurodegenerative diseases; Prion-like propagation; Seeding; Endocytosis; Endolyosomal leaking; Degradation
