What causes the death of dopaminergic neurons in Parkinson's disease?

摘要: The factors governing neuronal loss in Parkinson's disease (PD) are the subject of continuing speculation and experimental study. In recent years, that act on most or all cell types (pan-cellular factors), particularly genetic mutations environmental toxins, have dominated public discussions aetiology. Although there is compelling evidence supporting an association between risk these factors, pattern pathology difficult to explain without cell-specific factors. This chapter focuses studies showing neurons at greatest PD--substantia nigra pars compacta (SNc) dopamine (DA) neurons--have a distinctive physiological phenotype could contribute their vulnerability. opening L-type calcium channels during autonomous pacemaking results sustained entry into cytoplasm SNc DA neurons, resulting elevated mitochondrial oxidant stress susceptibility toxins used create animal models PD. increase negative consequences pan-cellular broadly challenge either proteostatic competence. availability well-tolerated, orally deliverable antagonists for points novel neuroprotective strategy complement current attempts boost function early stages disease.