Coevolution study of tau and a-synuclein suggests a connection between their normal interaction in neurons and the Parkinson's disease-associated mutation A53T

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James M Gruschus


Alpha-synuclein lies at the center of Parkinson’s disease etiology, and polymorphisms in the gene for the microtubule-associated protein tau are risk factors for getting the disease.  Tau and a-synuclein interact in vitro, and a-synuclein can also compete with tau binding to microtubules.  To test whether these interactions might be part of their natural biological functions, a correlated mutation analysis was performed between tau and a-synuclein, looking for evidence of coevolution.  For comparison, analyses were also performed between tau and b- and g-synuclein.  In addition, analyses were performed between tau and the synuclein proteins and the neuronal tubulin proteins. Potential correlated mutations were detected between tau and a-synuclein, one involving an a-synuclein residue known to interact with tau in vitro, Asn122, and others involving the Parkinson’s disease-associated mutation A53T. No significant correlated mutations were seen between tau and b- and g-synuclein.  Tau showed potential correlated mutations with the neuron-specific bIII-tubulin protein, encoded by the TUBB3 gene.  No convincing correlated mutations were seen between the synuclein and tubulin proteins, with the possible exception of b-synuclein with bIVa-tubulin, encoded by the TUBB4A gene.   While the correlated mutations between tau and a-synuclein suggest the two proteins have coevolved, additional study will be needed to confirm that their interaction is part of their normal biological function in cells.

Keywords: Correlated mutations analysis, mutual information, tauopathy, Alzheimer’s disease, axon, neurodegenerative, intrinsically disordered protein, protein-protein interaction

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GRUSCHUS, James M. Coevolution study of tau and a-synuclein suggests a connection between their normal interaction in neurons and the Parkinson's disease-associated mutation A53T. Medical Research Archives, [S.l.], v. 9, n. 7, july 2021. ISSN 2375-1924. Available at: <>. Date accessed: 04 june 2023. doi:
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