The misfolding and subsequent abnormal accumulation and aggregation of -Synuclein ( Syn) 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 Syn 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 Syn aggregation and misfolding, focusing on the contribution of TLRs to the progression of -synucleinopathies and speculating on their link with the non-motor disturbances associated with aging and neurodegenerative disorders.
Synucleinopathies Take Their Toll: Are TLRs a Way to Go?
Carmela Conte
Conceptualization
2023
Abstract
The misfolding and subsequent abnormal accumulation and aggregation of -Synuclein ( Syn) 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 Syn 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 Syn aggregation and misfolding, focusing on the contribution of TLRs to the progression of -synucleinopathies and speculating on their link with the non-motor disturbances associated with aging and neurodegenerative disorders.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.