This study points to C/EBPδ as an important repressor of SNCA transcription and suggests that reduced C/EBPδ neuronal levels could be a pathogenic factor in Parkinson's disease and other synucleinopathies and C/EBPδ activity a potential pharmacological target for these neurological disorders.
Alpha-Synuclein (AS) is the protein playing the major role in Parkinson's disease (PD), a neurological disorder characterized by the degeneration of dopaminergic neurons and the accumulation of AS into amyloid plaques.
Previously, we reported that intracranial inoculation of brain homogenate from multiple system atrophy (MSA) patient samples produces neurological disease in the transgenic (Tg) mouse model TgM83<sup>+/-</sup>, which uses the prion protein promoter to express human α-synuclein harboring the A53T mutation found in familial Parkinson's disease (PD).
Notably, manganese (Mn) exposure leads to a PD-like neurological disorder referred to as manganism-and induces pathogenic PTMs of α-synuclein and LRRK2.
Thirty-one patients with impulsive compulsive behaviours and Parkinson's disease who donated their brains to the Queen Square Brain Bank for Neurological Disorders were assessed for α-synuclein neuropathological load and tyrosine hydroxylase levels in the nucleus accumbens, dorsal putamen and caudate using immunohistochemistry.
Here, we investigated the potential of α-synuclein fibrils to induce neurological disease in TgM83<sup>+/-</sup> mice expressing the A53T mutant of human α-synuclein after oral or intravenous challenge and compared it to intraperitoneal and intracerebral challenge.
MSA prions are transmissible to transgenic (Tg) mice expressing mutated human α-synuclein (TgM83<sup>+/-</sup>), inducing neurological disease following intracranial inoculation with brain homogenate from deceased patient samples.
Almost 20 years after α-synuclein was discovered as the primary component of GCIs, α-synuclein aggregates isolated from MSA patient samples were shown to infect cultured mammalian cells and also to transmit neurological disease to transgenic mice.
There is increasing evidence for the contribution of synuclein alpha (<i>SNCA</i>) to the etiology of neurological disorders, such as Parkinson's disease (PD).
Synucleinopathies of the aging population are an heterogeneous group of neurological disorders that includes Parkinson's disease (PD) and dementia with Lewy bodies (DLB) and are characterized by the progressive accumulation of α-synuclein in neuronal and glial cells.
Here, we used structure-based computational methods to optimize the binding affinity of V<sub>H</sub>NAC1, a single-domain intracellular antibody (intrabody) from the camelid family that was selected for its specific binding to the nonamyloid component (NAC) of human α-synuclein (α-syn), a natively disordered protein, implicated in the pathogenesis of Parkinson's disease (PD) and related neurological disorders.
The aggregation of alpha-synuclein (αSyn) is the pathological hallmark of Parkinson's disease, dementia with Lewy bodies and related neurological disorders.
Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn).
The technology was first adapted with synthetic αSyn oligomers prepared in vitro and used to screen in 2 blinded cohorts of CSF samples from German and Japanese patients with PD (n = 76) and individuals serving as controls affected by other neurologic disorders (n = 65), neurodegenerative diseases (n = 18), and Alzheimer disease (n = 14).
Bioinformatics analyses revealed that most of the 166 brain substrates identified interacted with huntingtin, the amyloid precursor protein or α-synuclein and that neurological disease was the most significant canonical pathway associated with the substrates.
One such pathological condition is manifested in Parkinson's disease, the second most common neurological disorder in humans, which is characterized by the aggregation of the protein, α-synuclein.
Misfolding and aggregation of α-synuclein (α-syn) into Lewy bodies is associated with a range of neurological disorders, including Parkinson's disease (PD).
We utilized 769 controls without neurological disease (Mean age: 79 years, Range: 33-99 years) and examined the frequency of 20 different SNCA variants across age groups using logistic regression models.
Alpha-synuclein (AS) is an intrinsically unstructured protein in aqueous solution but is capable of forming beta-sheet-rich fibrils that accumulate as intracytoplasmic inclusions in Parkinson disease and certain other neurological disorders.
Excessive accumulation of alpha synuclein (a-syn) in the brain has been implicated in several degenerative neurological disorders, most notably Parkinson's disease.
alpha-Synucleinopathies are a group of neurological disorders characterized by the presence of intracellular inclusion bodies containing alpha-synuclein.
We analysed the association between degeneration and humoral immune markers in brain tissue of patients with idiopathic (n = 13) or genetic (n = 2 with alpha-synuclein and n = 1 with parkin mutations) Parkinson's disease and controls without neurological disease (n = 12) to determine the humoral immune involvement in Parkinson's disease.