title: Interaction between tau and alpha-synuclein proteins is impaired in the presence of P301L tau mutation.
abstract: Deposits of tau and alpha-synuclein are hallmarks of distinct neurodegenerative diseases: tauopathies and alpha-synucleinopathies. Affinity chromatography experiments demonstrated a direct binding of the two proteins, and alpha-synuclein was shown to induce fibrillization of tau. Here, we verify the presence of this physical interaction by using different cellular systems. This binding was abolished by the most common tau mutation (P301L) associated with frontotemporal dementia. We restored the impaired interaction by inducing heat shock proteins 70 and 90. In addition, we show that P301L tau mutation strongly affects tau and alpha-synuclein neuronal distribution.
authors.affiliation: NeuroBioGen Lab-Memory Clinic, IRCCS Centro S. Giovanni di Dio-FBF, via Pilastroni 4, 25123 Brescia, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Benussi
authors.forename: Roberta
authors.initials: R
authors.lastname: Ghidoni
authors.forename: Anna
authors.initials: A
authors.lastname: Paterlini
authors.forename: Francesca
authors.initials: F
authors.lastname: Nicosia
authors.forename: Antonella C
authors.initials: AC
authors.lastname: Alberici
authors.forename: Simona
authors.initials: S
authors.lastname: Signorini
authors.forename: Laura
authors.initials: L
authors.lastname: Barbiero
authors.forename: Giuliano
authors.initials: G
authors.lastname: Binetti
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection; D020798:Two-Hybrid System Techniques; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C118958:SNCAIP protein, human; D016875:tau Proteins; D005982:Glutathione Transferase