Title:Bringing the Spotlight to Tau and TDP-43 in Frontotemporal Dementia:
A Review of Promising Chemical Compounds
Volume: 29
Issue: 38
Author(s): Karla Villalobos-Nova, Sebastián Monroy-Moya, Joaquín Maulen-Peñaloza, Gabriela C.M. Pinto and Alberto Cornejo*
Affiliation:
- Departmento Tecnología Médica, Universidad Andrés Bello, Universidad Andrés Bello, Echaurren 183Santiago,
Chile
Keywords:
Frontotemporal dementia, proteinopathies, tau, TDP-43, protein aggregation, chemical compounds.
Abstract: There is a wide variety of neurodegenerative diseases, among which frontotemporal
dementia stands out. These are the second most frequent cause of dementia in the
world and demand the search for an effective treatment. This disease is linked to the abnormal
behavior of proteins, which group together to form insoluble aggregates. It has
been shown that the tau protein and TDP-43 are the main proteins involved in these
pathologies. This article details 11 compounds already used in different neuropathologies,
which may serve as potential drugs against these proteins. The mechanism of how
most of these molecules inhibited the tau and TDP-43 aggregation process was highlighted.
Importantly, Curcumin, Proanthocyanidin B2, Oleocanthal, Oleuropein Aglycone,
Thionine, and Resveratrol had been reported as direct inhibitors of tau. While 4-aminoquinoline,
Dimethoxycurcumin, and Auranofin directly inhibited TDP-43. Epigallocatechin-
3- gallate and Methylene Blue were described as tau and TDP-43 inhibitors. In this
review, it is proposed that future research could elucidate the detailed inhibition mechanisms
of these compounds to obtain relevant data to advance in treatments search for these
coexisting proteins in frontotemporal dementia.
