What are alpha synuclein oligomers?
Alpha-Synuclein Oligomers—Neurotoxic Molecules in Parkinson’s Disease and Other Lewy Body Disorders. Adverse intra- and extracellular effects of toxic α-synuclein are believed to be central to the pathogenesis in Parkinson’s disease and other disorders with Lewy body pathology in the nervous system.
What is alpha synuclein structure?
α-Syn is a small acidic protein with three domains namely N-terminal lipid-binding α-helix, amyloid-binding central domain (NAC), and C-terminal acidic tail.
What are alpha synuclein aggregates?
Alpha-synuclein (αS) aggregation participates in neurodegenerative maladies including Parkinson’s disease (PD), multiple system atrophy, and dementia with Lewy bodies, but there is no consensus on what mechanisms trigger aggregation, neuronal cell loss, and degeneration.
How does a synuclein aggregate?
Mechanisms of α-synuclein aggregation and propagation Unfolded monomers of α-synuclein (α-syn) interact to form two types of dimers: anti-parallel dimers, which do not propagate, and parallel dimmers, which do propagate. A dynamic equilibrium is established between unfolded monomers and both forms of dimers.
What is the role of alpha synuclein?
Alpha-synuclein is a neuronal protein that regulates synaptic vesicle trafficking and subsequent neurotransmitter release. It is abundant in the brain, while smaller amounts are found in the heart, muscle and other tissues.
How is alpha synuclein toxic?
α-synuclein toxicity is commonly modeled by the overexpression of wild-type α-synuclein, expression of PD-linked α-synuclein mutations, injection or incubation with α-synuclein preformed oligomers or fibrils or targeted expression of α-synuclein using AAV.
What is alpha-synuclein made of?
The human alpha-synuclein protein is made of 140 amino acids. An alpha-synuclein fragment, known as the non-Abeta component (NAC) of Alzheimer’s disease amyloid, originally found in an amyloid-enriched fraction, was shown to be a fragment of its precursor protein, NACP.
What is alpha-synuclein and Parkinson’s disease?
Alpha-synuclein (α-Syn) is a key protein involved in Parkinson’s disease (PD) pathology. PD is characterized by the loss of dopaminergic neuronal cells in the substantia nigra pars compacta and the abnormal accumulation and aggregation of α-Syn in the form of Lewy bodies and Lewy neurites.
What is the function of alpha-synuclein?
What cells express alpha-synuclein?
α-Synuclein is widely expressed in the brain, in both neuronal and nonneuronal cell types, including dopaminergic neurons, cortical neurons, noradrenergic neurons, endothelial cells, and platelets [62–64].
What causes alpha-synuclein aggregate?
Impairments in mitochondrial function or an increase in oxidative stress can induce protein modifications that facilitate the conversion of α-synuclein to a fibrillar pathway. Changes in membrane composition or changes in expression of binding partners can initiate α-synuclein aggregation.
Is alpha-synuclein a membrane protein?
With only 140 amino acids, α-Synuclein (α-Syn) is a small peripheral membrane protein that localizes specifically to the axon terminal in neurons (Maroteaux et al., 1988; George et al., 1995; Iwai et al., 1995; Bendor et al., 2013).
What are the monomers and Dimers of α-synuclein?
Samples of α-synuclein monomers (αS-1), tandem dimers (αS-2), tandem tetramers (αS-4), and tandem octamers (αS-8) were expressed, purified, and labelled fluorescently at the C terminus with either green or red dyes as described in the Methods section.
Which is the most toxic form of alpha synuclein?
IHC analysis of rat brain injected with Type 1 mouse alpha synuclein PFFs (SPR-324) shows alpha synuclein pathology. Alpha synuclein oligomers are increasingly thought to be the toxic species in synucleinopathies. Dopamine and EGCG can be used to stabilize alpha synuclein in its oligomeric forms, preventing further aggregation into fibrils.
Are there any monomers or PFFS for alpha synuclein?
A53T alpha synuclein monomers and PFFs are also available. The A53T mutation has been linked to early-onset Parkinson’s Disease and increased alpha synuclein fibrillization. IHC analysis of rat brain injected with Type 1 mouse alpha synuclein PFFs (SPR-324) shows alpha synuclein pathology.
How are oligomers and monomers related in aggregation?
Measuring the extent of association between oligomeric species of different sizes at various points during the earliest stages of aggregation, we found that the tandem oligomers preferentially self-associated rather than acting as seeds to accelerate the addition of monomers.