Bringing the Spotlight to Tau and TDP-43 in Frontotemporal Dementia:
A Review of Promising Chemical Compounds

Karla      Villalobos-Nova; Sebastián      Monroy-Moya; Joaquín      Maulen-Peñaloza; Gabriela   C.M.   Pinto; Alberto      Cornejo
doi:10.2174/0929867329666220508175340
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.
Keywords: Frontotemporal dementia, proteinopathies, tau, TDP-43, protein aggregation, chemical compounds.
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DOI https://dx.doi.org/10.2174/0929867329666220508175340	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

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