Alpha Synuclein TNG (A53T, S87N, N103G) Mutant Monomers

Human alpha synuclein TNG mutant (HuTNG) is a triple mutant containing Ala53 mutated to the equivalent mouse residue Thr53, Ser87 mutated to the equivalent mouse residue Asn87, and Asn103 mutated to the equivalent mouse residue Gly103, effectively making it a human-mouse chimeric protein. Despite sequence differences at only seven residues, or 5% of the total 140 amino acids, the aggregation rate of wild-type mouse α-syn (MsWT) is faster than wild-type human α-syn (HuWT) in vitro. In wild-type mouse models, MsWT fibrils are more efficient than HuWT fibrils at inducing endogenous mouse α-syn pathology (1) . A53T or S87N substitutions in human α-syn substantially accelerate fibrilization rates in vitro (2,3) . Chimeric HuTNG fibrils show enhanced induction of α-syn pathology greater than both HuWT and MsWT fibrils after single unilateral injection into the dorsal striatum in mice (4) . Therefore, HuTNG is a good construct for inducing robust endogenous α-syn seeding and pathology in wild-type mice.

Alpha synuclein protein, Alpha-synuclein protein, Non-A beta component of AD amyloid protein, Non-A4 component of amyloid precursor protein, NACP protein, SNCA protein, NACP protein, PARK1 protein, SYN protein, Parkinson's disease familial 1 Protein, Alpha Synuclein TNG

Neuroscience | Neurodegeneration | Alzheimer's Disease | Tangles & Tau | Neuroscience | Neurodegeneration | Parkinson's Disease | Synuclein | Neuroscience | Neurodegeneration | Multiple System Atrophy

1. Masuda-Suzukake et al. 2013. Prion-like Spreading of Pathological α-synuclein in Brain. Brain. https://doi.org/10.1093/braiwt037 2. Kang, K. et al. 2011. The A53T Mutation is Key in Defining the Differences in the Aggregation Kinetics of Human and Mouse α-synuclein. JACS. https://doi.org/10.1021/ja203979j 3. Ohgita, T. et al. 2023. Intramolecular Interaction Kinetically Regulates Fibril Formation by Human and Mouse Alpha-Synuclein. Sci Rep https://doi.org/10.1038/s41598-023-38070-4 4. Luk, K., C. et al. 2016. Molecular and Biological Compatibility with Host Alpha-Synuclein Influences Fibril Pathogenicity. Cell Rep. https://doi.org/10.1016/j.celrep.2016.08.053

1. Masuda-Suzukake et al. 2013. Prion-like Spreading of Pathological α-synuclein in Brain. Brain. https://doi.org/10.1093/brain/awt037 2. Kang, K. et al. 2011. The A53T Mutation is Key in Defining the Differences in the Aggregation Kinetics of Human and Mouse α-synuclein. JACS. https://doi.org/10.1021/ja203979j 3. Ohgita, T. et al. 2023. Intramolecular Interaction Kinetically Regulates Fibril Formation by Human and Mouse Alpha-Synuclein. Sci Rep https://doi.org/10.1038/s41598-023-38070-4 4. Luk, K., C. et al. 2016. Molecular and Biological Compatibility with Host Alpha-Synuclein Influences Fibril Pathogenicity. Cell Rep. https://doi.org/10.1016/j.celrep.2016.08.053