α-synuclein abnormalities trigger focal tau pathology, spreading to various brain areas in Parkinson disease.
J Neurochem
; 157(3): 727-751, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33264426
ABSTRACT
Parkinson disease (PD) is the second most common neurodegenerative disorder, whose prevalence is 2~3% in the population over 65. α-Synuclein aggregation is the major pathological hallmark of PD. However, recent studies have demonstrated enhancing evidence of tau pathology in PD. Despite extensive considerations, thus far, the actual spreading mechanism of neurodegeneration has remained elusive in a PD brain. This study aimed to further investigate the development of α-synuclein and tau pathology. We employed various PD models, including cultured neurons treated with either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or with recombinant α-synuclein. Also, we studied dopaminergic neurons of cytokine Interferon-ß knock-out. Moreover, we examined rats treated with 6-hydroxydopamine, Rhesus monkeys administrated with MPTP neurotoxin, and finally, human post-mortem brains. We found the α-synuclein phosphorylation triggers tau pathogenicity. Also, we observed more widespread phosphorylated tau than α-synuclein with prion-like nature in various brain areas. We optionally removed P-tau or P-α-synuclein from cytokine interferon-ß knock out with respective monoclonal antibodies. We found that tau immunotherapy suppressed neurodegeneration more than α-synuclein elimination. Our findings indicate that the pathogenic tau could be one of the leading causes of comprehensive neurodegeneration triggered by PD. Thus, we can propose an efficient therapeutic target to fight the devastating disorder.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Encéfalo
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Tauopatias
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Alfa-Sinucleína
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Female
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Humans
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Male
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Pregnancy
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Irã