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.
2023
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/1549213
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