The role of LRRK2 on PKA-NFκB pathway in microglia cells: implications for Parkinson’s disease
Isabella Russo
摘要：Leucine-rich repeat kinase 2 (LRRK2), a gene linked to autoso-mal-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 sev-eral molecular pathways important for neuronal activity (Martin et al., 2014), the observation that its expression is high in mi-croglia has attracted the attention of different groups to under-stand 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 mi-croglia activation and plays important roles in these cells (Rus-so et al., 2014). 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 mole-cules, which results in deleterious cellular damage, as observed in different neurodegenerative diseases including PD (Tansey and Goldberg, 2010).
机标关键词：
资助基金：by the Intramural Research program of the NIH and Umberto Veronesi post-doctoral fellowship year 2015 and 2017 Award(693 and 1395)
论文发表日期：2019-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：2( 1713-1714 )