中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (1): 125-126.doi: 10.4103/1673-5374.343895

• 观点:退行性病与再生 • 上一篇    下一篇

关于帕金森病中的神经退行性变和神经炎症的错综复杂的辩论:哪个先出现?

  

  • 出版日期:2023-01-15 发布日期:2022-06-17

The intricate debate on neurodegeneration and neuroinflammation in Parkinson’s disease: which came first?

Antonella Cardinale*, #, Valeria Calabrese*, #   

  1. Experimental Neurophysiology Laboratory, IRCCS San Raffaele Roma, Rome, Italy (Cardinale A, Calabrese V)
    Department of Medicine, Università degli Studi di Perugia, Perugia, Italy (Calabrese V)
  • Online:2023-01-15 Published:2022-06-17
  • Contact: Antonella Cardinale, PhD, antonella.cardinale@sanraffaele.it; Valeria Calabrese, PhD, valeria.calabrese@sanraffaele.it.
  • Supported by:
    This work was supported by a grant from NYU Grossman School of Medicine and The Marlene and Paolo Fresco Institute for Parkinson’s and Movement Disorders, which was made possible with support from Marlene and Paolo Fresco (to AC).

摘要: https://orcid.org/0000-0002-3185-1006 (Antonella Cardinale)
https://orcid.org/0000-0002-1127-1741 (Valeria Calabrese)

Abstract: Parkinson’s disease (PD) is a heterogeneous multifactorial disorder and, during the last years, new scientific evidence has supported this concept. The principal hallmarks of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta and the aggregation of misfolded alpha-synuclein (α-syn). In particular, α-syn is receiving great attention for its key role in PD neuropathology. Both genetic mutations and post-translational modifications (i.e., α-syn phosphorylation) can induce protein misfolding. An abnormal accumulation of this misfolded α-syn crushes both the ubiquitin-proteosome and autophagy systems, which are involved in protein clearance. As a result, α-syn aggregation leads to neuronal dysfunction and neurodegeneration. Along with this pathological condition, dysregulated mitochondrial activity, reactive oxygen species production, oxidative stress, and blood-brain barrier alteration, are typical features of neurological disorders such as PD. In addition, neuroinflammatory processes are critical for PD pathogenesis and strictly interconnected to α-syn pathology. According to this, neuroinflammation could be considered as a potential early drug target.