中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (10): 1713-1714.doi: 10.4103/1673-5374.257523

• 观点:退行性病与再生 • 上一篇    下一篇

富含亮氨酸重复激酶2对小胶质细胞蛋白激酶A-核因子-κB途径的影响:对帕金森病的意义

  

  • 出版日期:2019-10-15 发布日期:2019-10-15

The role of LRRK2 on PKA-NFκB pathway in microglia cells: implications for Parkinson’s disease

Isabella Russo   

  1. Biology and Genetic Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
  • Online:2019-10-15 Published:2019-10-15
  • Contact: Isabella Russo, PhD, isabella.russo@unibs.it.
  • Supported by:

    This work was supported by Michael J Fox Foundation, InCure (EU Joint Programme – Neurogenerative Disease Research, JPND), by the University of Padova (STARS Grants, LRRKing-Role of the Parkinson’s disease kinase LRRK2 in shaping neurites and synapses), by the Intramural Research program of the NIH and Umberto Veronesi post-doctoral fellowship year 2015 and 2017 Award (693 and 1395).

摘要:

orcid: 0000-0002-6151-2451 (Isabella Russo)

Abstract:

Leucine-rich repeat kinase 2 (LRRK2), a gene linked to autosomal-dominantly inherited and sporadic Parkinson’s disease (PD) as a risk factor, encodes a large and complex protein with a dual enzymatic activity. LRRK2 contains several domains involved in protein-protein interactions, however, the presence of both a kinase and GTPase domain points to intracellular signaling functions (Marín, 2006). While LRRK2 has been linked to several molecular pathways important for neuronal activity, the observation that its expression is high in microglia has attracted the attention of different groups to understand whether LRRK2 dysfunctions in these cells may impact neuronal activity as secondary event. In this regard, since 2012 numerous studies have demonstrated that LRRK2 controls microglia activation and plays important roles in these cells. Microglia are highly specialized macrophages responsible for mediating innate immune defense in the brain and scavenging debris or misfolded/aggregated proteins. They are considered main actors upon an inflammatory stimulus, and although a well-regulated inflammatory response is crucial for tissue repair and brain homeostasis, an excessive and prolonged neuroinflammation can lead to overproduction of toxic molecules, which results in deleterious cellular damage, as observed in different neurodegenerative diseases including PD.