Methylene blue and dimebon inhibit aggregation of TDP-43 in cellular models.
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) are major neurodegenerative diseases with TDP-43 pathology. Here we investigated the effects of methylene blue (MB) and dimebon, two compounds that have been reported to be beneficial in phase II clinical trials of Alzheimer's disease (AD), on the formation of TDP-43 aggregates in SH-SY5Y cells. Following treatment with 0.05 microM MB or 5 microM dimebon, the number of TDP-43 aggregates was reduced by 50% and 45%, respectively. The combined use of MB and dimebon resulted in a 80% reduction in the number. These findings were confirmed by immunoblot analysis. The results indicate that MB and dimebon may be useful for the treatment of ALS, FTLD-U and other TDP-43 proteinopathies.
Yamashita
Makiko
M
Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Reearch, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.
Nonaka
Takashi
T
Arai
Tetsuaki
T
Kametani
Fuyuki
F
Buchman
Vladimir L
VL
Ninkina
Natalia
N
Bachurin
Sergey O
SO
Akiyama
Haruhiko
H
Goedert
Michel
M
Hasegawa
Masato
M
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002460:Cell Line / Q000187:drug effects* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D002479:Inclusion Bodies / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007211:Indoles / Q000494:pharmacology*; D008751:Methylene Blue / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D007211:Indoles; C010119:latrepirdine; D008751:Methylene Blue