The accumulation and aggregation of alpha-synuclein(α-syn)in several tissue including the brain is a major pathological hallmark in Parkinson’s disease(PD).In this study,we show that α-syn can be taken up by primar...The accumulation and aggregation of alpha-synuclein(α-syn)in several tissue including the brain is a major pathological hallmark in Parkinson’s disease(PD).In this study,we show that α-syn can be taken up by primary human cortical neurons,astrocytes and skin-derived fibroblasts in vitro.Our findings that brain and peripheral cells exposed to α-syn can lead to impaired mitochondrial function,leading to cellular degeneration and cell death,provides additional evidence for the involvement of mitochondrial dysfunction as a mechanism of toxicity of α-syn in human cells.展开更多
In this mini-review,we summarize recent findings relating to the prion-like propagation ofα-synuclein(α-syn)and the development of novel therapeutic strategies to target synucleinopathy in Parkinson’s disease(PD).W...In this mini-review,we summarize recent findings relating to the prion-like propagation ofα-synuclein(α-syn)and the development of novel therapeutic strategies to target synucleinopathy in Parkinson’s disease(PD).We link the Braak’s staging hypothesis of PD with the recent evidence from in-vivo and in-vitro studies for the prion-like cell-to-cell propagation ofα-syn(via exocytosis and endocytosis).The classical accumulation of aggregatedα-syn in PD may result from an increased production or a failure in the mechanisms of clearance ofα-syn.We discuss novel agents,currently in clinical trial for PD including the ones that impact the aggregation ofα-syn and others that interfere withα-syn endocytosis as a means to target the progression of the disease.展开更多
基金This work was supported by the UNSW Faculty of Medicine Research Grant to Dr Nady BraidyDr Nady Braidy is also the recipient of an Alzheimer’s Australia Viertel Foundation and the National Health and Medical Research Council Early Career Research Fellowship at the University of New South Wales.This work has been also supported by the Alzheimer’s Association(grant#IIRG-08–89545)the Rebecca Cooper foundation(Australia).
文摘The accumulation and aggregation of alpha-synuclein(α-syn)in several tissue including the brain is a major pathological hallmark in Parkinson’s disease(PD).In this study,we show that α-syn can be taken up by primary human cortical neurons,astrocytes and skin-derived fibroblasts in vitro.Our findings that brain and peripheral cells exposed to α-syn can lead to impaired mitochondrial function,leading to cellular degeneration and cell death,provides additional evidence for the involvement of mitochondrial dysfunction as a mechanism of toxicity of α-syn in human cells.
文摘In this mini-review,we summarize recent findings relating to the prion-like propagation ofα-synuclein(α-syn)and the development of novel therapeutic strategies to target synucleinopathy in Parkinson’s disease(PD).We link the Braak’s staging hypothesis of PD with the recent evidence from in-vivo and in-vitro studies for the prion-like cell-to-cell propagation ofα-syn(via exocytosis and endocytosis).The classical accumulation of aggregatedα-syn in PD may result from an increased production or a failure in the mechanisms of clearance ofα-syn.We discuss novel agents,currently in clinical trial for PD including the ones that impact the aggregation ofα-syn and others that interfere withα-syn endocytosis as a means to target the progression of the disease.
