Synucleinopathies Take Their Toll: Are TLRs a Way to Go?

卷:12

Review

关键词: GLIAL CYTOPLASMIC INCLUSIONS;    ALPHA-SYNUCLEIN;    PARKINSONS-DISEASE;    OXIDATIVE STRESS;    RECEPTOR 2;    MITOCHONDRIAL DYSFUNCTION;    DROSOPHILA MODEL;    CIRCADIAN CLOCK;    AGGREGATION;    BRAIN;   

DOI  :  10.3390/cells12091231

来源: SCIE

【 摘 要 】

The misfolding and subsequent abnormal accumulation and aggregation of a-Synuclein (aSyn) as insoluble fibrils in Lewy bodies and Lewy neurites is the pathological hallmark of Parkinson's disease (PD) and several neurodegenerative disorders. A combination of environmental and genetic factors is linked to aSyn misfolding, among which neuroinflammation is recognized to play an important role. Indeed, a number of studies indicate that a Toll-like receptor (TLR)-mediated neuroinflammation might lead to a dopaminergic neural loss, suggesting that TLRs could participate in the pathogenesis of PD as promoters of immune/neuroinflammatory responses. Here we will summarize our current understanding on the mechanisms of aSyn aggregation and misfolding, focusing on the contribution of TLRs to the progression of a-synucleinopathies and speculating on their link with the non-motor disturbances associated with aging and neurodegenerative disorders.