Accumulation of <alpha>-synuclein (<alpha>-syn) positive protein aggregates in the substantia nigra is a pathological hallmark of PD, indicating that protein turnover defect is implicated in PD pathogenesis.
Rats and mice with unilateral damage to the nigrostriatal dopamine system-induced by neurotoxins, such as 6-hydroxydopamine, overexpression of α-synuclein, or injections of toxic synuclein protofibrils-are widely used as experimental models to mimic the loss of dopamine neurons seen in Parkinson's disease.
We are witnessing exciting times, with the first clinical trials being conducted that target synuclein, and bring the hope of novel therapies for patients with PD and their families.
Tyrosine hydroxylase (TH) was increased significantly and <i>α</i>-synuclein protein expression was reduced in the EX-PD group compared to the SED-PD group.
This study suggests that chronic intermittent hypoxia can increase the <i>α</i>-synuclein levels, which may contribute to the pathogenesis of Parkinson's disease.
The etiology of Parkinson's disease (PD) is linked with cellular inclusions in the <i>substantia nigra pars compacta</i> region of the brain that are enriched in the misfolded presynaptic protein <i>α</i>-synuclein (<i>α</i>S) and death of the dopaminergic neurons.
In addition, this review discusses the events of cross presentation of synuclein peptides by professional antigen presenting cells and microglia, induction of inflammatory responses in the periphery and brain, and emerging calpain-targeted therapeutic strategies to attenuate neuronal death in PD.
The results revealed that treatment with 7,8-DHF improved PD model's behavioral performance and reduced dopaminergic neuron loss in the SN and striatum, associated with the activation of TrkB receptors and its signaling cascades, and reduced <i>p</i>-MAPK, <i>p</i>-<i>α</i>-synuclein, and <i>p</i>-tau.
Dopaminergic neurons differentiated by transcription factor expression showed aggravated neurodegeneration through α-synuclein overexpression, but were not sensitive to γ-synuclein overexpression, suggesting that these neurons are well suited to study neurodegeneration in the context of Parkinson's disease.
Evidence suggests that various forms of <i>α</i>-synuclein- (<i>α</i>Syn-) mediated microglial activation are associated with the progression of Parkinson's disease.
The effects of stable overexpression of γ-synuclein (γ-syn), a neuronal protein recently recognized as a novel regulator of lipid handling in adipocytes, and transient overexpression of Parkinson's disease (PD) α-synuclein [α-syn; wild-type (wt) and its pathogenic mutants A53T, A30P and E46K] in SH-SY5Y and T98G cells, were also evaluated.
miR-486-3p Influences the Neurotoxicity of a-Synuclein by Targeting the SIRT2 Gene and the Polymorphisms at Target Sites Contributing to Parkinson's Disease.
For example, epigenetic alterations of the gene encoding for <i>α</i>-synuclein (<i>SNCA</i>) have been widely explored in both brain and peripheral tissues of Parkinson's disease samples.
The presence of RBD in PD is associated with faster motor progression in patients with greater synuclein and dopaminergic pathology, and with higher risk of cognitive decline in patients with greater synuclein and amyloid pathology.
The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects.
The study aims to investigate whether Long non-coding RNA (LncRNA)-UCA1 can regulate the progression of Parkinson's disease (PD) by mediating a-synuclein (SNCA) expression.
The synuclein family is composed of three members, two of which, α- and β-synuclein, play a major role in the development of synucleinopathies, including Parkinson's disease (PD) as most important movement disorder, dementia with Lewy bodies (DLB) as the second most frequent cause of dementia after Alzheimer's disease and multiple system atrophy.