Lewy body diseases such as Parkinson disease (PD) involve intra-neuronal deposition of the protein alpha-synuclein (AS) and depletion of nigrostriatal dopamine.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the gradual appearance of α-synuclein (α-syn)-containing neuronal protein aggregates.
Our study provides high-resolution insights into the structure of the PD-associated protein α -synuclein in complex with the most abundant cellular cyclophilin.
Genetic forms represent a small fraction of Parkinson's disease (PD) but their discovery has revolutionized research in the field, putting α-synuclein in the spotlight, and uncovering other key neuropathological mechanisms of the disease.
It has been suggested that extracellular alpha synuclein (αSyn) can mediate neuroinflammation in Parkinson's disease, and that αSyn affects B-cell maturation.
Prominent examples are amyloid beta and tau in Alzheimer's disease, α-synuclein in Parkinson's disease and transactive response DNA binding protein 43 kDa (TDP-43) in ALS and FTD.
This work reports identification of the catabolic pathway of oligomeric α-synuclein as well as showing how Omi functions as the key molecule in the recognition and degradation of toxic oligomeric α-synuclein, a possible cause of neurodegeneration in PD, without affecting monomeric α-synuclein which is a native essential molecule for the normal function of neurons.
Although presenting with distinct pathological hallmarks, which in MSA consist of glial cytoplasmic inclusions (GCIs) containing fibrillar α-synuclein in oligodendrocytes, both MSA and Parkinson's disease are α-synucleinopathies.
Activation of autophagic pathways to reduce aged-related accumulation of pathogenic SNCA oligomers is a viable disease-modifying therapeutic strategy for PD.
N-acetylated α-synuclein (αSyn) has long been established as an intrinsically disordered protein associated with a dysfunctional role in Parkinson's disease.
Furthermore, to enhance the pathological properties of α-synuclein, we inserted into SNCA an A53T mutation, two single-nucleotide polymorphisms identified in a genome-wide association study in Parkinson's disease and a Rep1 polymorphism, all of which are causal of familial Parkinson's disease or increase the risk of sporadic Parkinson's disease.
The myriad posttranslational modifications that occur on several of the amyloid forming proteins, including the Parkinson's disease causing protein α-synuclein, may be one such cause.
Lewy pathology, composed of α-Synuclein (α-Syn) inclusions, a hallmark of Parkinson's disease (PD), progressively spreads from the enteric nervous system (ENS) to the central nervous system (CNS).
Parkinson's disease (PD) is pathologically characterized by intraneuronal α-synuclein (α-Syn) aggregates called Lewy bodies (LBs) as well as the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc).
Administration of BM suppressed the level of pro-inflammatory cytokines, decreased the levels of α-synuclein, and reduced reactive oxygen species (ROS) generation in PD animal model.
DOPAL and α-synuclein are both found in dopaminergic neurons, where their levels are elevated in PD and in animal models exposed to chemical toxicants, including agricultural pesticides.