Alpha-synuclein overexpressing neurons are disease model neurons that overexpress the SNCA gene encoding the alpha-synuclein protein. These models replicate the proteinaceous inclusions known as Lewy bodies and Lewy neurites, which are pathological hallmarks of Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). These neurons are typically generated through viral vector-mediated gene delivery or derived from iPSCs carrying SNCA duplication/triplication mutations. [1]
| Property | Value | [2]
|----------|-------| [3]
| Category | Disease Model Neurons | [4]
| Location | Substantia nigra, cortex, other brain regions (model) | [5]
| Cell Types | AAV-Syn overexpression, iPSC-derived SNCA triplication neurons |
| Primary Neurotransmitter | Dopamine (nigral), Glutamate (cortical) |
| Key Markers | Alpha-synuclein, Phospho-Ser129, TH, NeuN |
| Taxonomy | ID | Name / Label |
|---|---|---|
| Cell Ontology (CL) | CL:0004117 | retinal ganglion cell A |
| Database | ID | Name | Confidence |
|---|---|---|---|
| Cell Ontology | CL:0004117 | retinal ganglion cell A | Medium |
Alpha-synuclein is a 140-amino acid protein predominantly expressed in presynaptic terminals. Its normal functions include:
In disease states, alpha-synuclein undergoes:
Soluble oligomeric forms of alpha-synuclein are considered the most toxic species:
Alpha-synuclein pathology can spread via:
Alpha-synuclein overexpressing neurons enable study of:
These models enable:
Phospho-Ser129: Pathological alpha-synuclein marker
Total alpha-synuclein: CSF and blood biomarker
Oligomeric alpha-synuclein: Toxic species detection
Neurofilament light chain: Neurodegeneration marker
Alpha-Synuclein SNCA Gene
Dopamine Neurons
Lewy Bodies
The study of Alpha Synuclein Overexpressing Neurons has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Spillantini MG, et al. Alpha-synuclein in Lewy bodies. Nature. 1997. 1997. ↩︎
Lashuel HA, et al. [The many faces of alpha-synuclein: from structure to neurotoxicity. J Mol Biol. 2002](https://doi.org/10.1016/S0022-2836(02). 2002. ↩︎
Kalia LV, et al. [Parkinson's disease. Lancet. 2015](https://doi.org/10.1016/S0140-6736(14). 2015. ↩︎
Prusiner SB, et al. Evidence for alpha-synuclein prions causing multiple system atrophy in humans. Proc Natl Acad Sci. 2018. 2018. ↩︎
Venda LL, et al. Alpha-synuclein and dopamine at the crossroads of Parkinson's disease. Trends Neurosci. 2010. 2010. ↩︎