Agonist activation of D3R increases dopamine concentration, decreases α-Syn accumulation, enhances secretion of brain derived neurotrophic factors (BDNF), ameliorates neuroinflammation, alleviates oxidative stress, promotes neurogenesis in the nigrostriatal pathway, interacts with D1R to reduce PD associated motor symptoms and ameliorates side effects of levodopa (L-DOPA) treatment.
After a mean follow-up of 3.5 ± 2.1 years, PD patients with baseline pS129-α-synuclein > 8.5 fg/mL were at higher risk of motor symptom progression of at least 3 points in the MDS-UPDRS part III scores than those with pS129-α-synuclein < 8.5 fg/mL (<i>p</i> = 0.03, log rank test).
Deletion and/or deficiency of α-synuclein does not influence clinical and neuropathological disease progression in murine MPS IIIA, demonstrating that in and of itself, this protein does not initiate the cognitive and motor symptoms that occur in the first 5 months of life in MPS IIIA mice.
During the course of disease, misfolded α-synuclein, the major constituent of LB, spreads to different regions of the brain in a prion-like fashion, giving rise to successive non-motor and motor symptoms.
Our study shows for the first time that SNCArs11931074 polymorphism might modulate brain functional alterations and correlate with motor symptoms in Chinese PD patients.
The presence of serotonergic pathology in premotor A53TSNCA carriers preceded development of dopaminergic pathology and motor symptoms and was associated with disease burden, highlighting the potential early role of serotonergic pathology in the progression of Parkinson's disease.
α-synuclein aggregation is hypothesised to start in autonomic nerve terminals years before the appearance of motor symptoms, and subsequently spread via autonomic nerves to the spinal cord and brainstem.
By using the in situ proximity ligation assay (PLA), which allows for the visualization of protein-protein interactions in tissues to detect dopamine transporter (DAT)/α-synuclein complexes, we previously described that these are markedly redistributed in the striatum of human α-synuclein transgenic mice at the phenotypic stage, showing dopamine (DA) release impairment without a DAT drop and motor symptoms.
The aim of this study was to investigate if plasma ASN level may be a valuable biomarker, is the level of plasma ASN concentration different in various motor subtypes of diseases, is there a relation between the level of plasma ASN and the severity of motor symptoms.
Parkinson's disease is a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, pathological accumulation of alpha-synuclein and motor symptoms, but also by non-motor symptoms.
A protein known as alpha-synuclein accumulates in brains of people with Parkinson's disease that is also present in the GI before the onset of motor symptoms.
Although there was a significant increase in plasma α-synuclein levels in PD patients with a higher Hoehn-Yahr (H-Y) stage, there was no correlation with motor symptom severity, as assessed by Unified Parkinson's Disease Rating Scale part III scores, after confounders (age, gender, and disease duration) were taken into account.
In the present study, we evaluated the roles of non-motor symptoms and signs and imaging biomarkers of nigral neuronal changes and α-synuclein accumulation in the colon.
Parkinson's disease, neuropathologically defined by the aggregation of α-synuclein, is characterized by neuropsychiatric symptoms such as depression and anxiety preceding the onset of motor symptoms.
The associations of hyposmia with SNCA variants and disease phenotypic characteristics including motor symptoms (UPDRS motor score) and other common NMSs (clinical possible RBD-cpRBD, depression and chronic constipation) were analyzed.
These data provide an insight into the physiological function of α-SYN in NErgic neuronal cells, which further indicates that the α-SYN mutation may play a causative role in the generation of non-motor symptoms in PD.
We recruited Parkinson's patients from the communities of three central California counties to investigate the influence of SNCA genetic variants on motor symptom progression in idiopathic PD.
Although there is a relationship, albeit not causal, between motor symptoms and the presence of Lewy bodies (LBs) and neurites filled with abnormal α-synuclein, other neurological alterations are independent of the amount of α-synuclein inclusions in neurons and neurites, thereby indicating that different mechanisms probably converge in the degenerative process.
Although the overabundance of human alpha-synuclein in nigral dopaminergic neurons is considered to play a pathogenic role in Parkinson's disease (PD), it remains unclear how alpha-synuclein leads to neuronal degeneration and motor symptoms.
These results demonstrate that a copy number variation of the SNCA gene is associated with selective impairments on reinforcement learning in asymptomatic carriers without the motor symptoms of Parkinson disease.