{"doi":"10.18103/mra.v9i7.2497","title":"Coevolution study of tau and a-synuclein suggests a connection between their normal interaction in neurons and the Parkinson's disease-associated mutation A53T","abstract":"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.","journal":"Medical Research Archives","year":2021,"id":225745,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.961,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":795062,"name":"James M. Gruschus","orcid":"0000-0002-2815-8542","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":null,"created_at":"2026-07-18T23:54:30.292454Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}