Table 4.

Therapeutic approaches to ameliorate toxicity of TDP-43 CTFs

Approach	Category	Mechanism of action	Reference
Raloxifene	Small molecule	Limits TDP-25 toxicity through autophagy	(Zhou et al., 2018)
Valproate	Small molecule	Attenuates TDP-25 toxicity mediated by ER stress and autophagy	(Wang et al., 2015b)
HSF1 overexpression	Transcription factor	Reduces TDP-35 levels, even after proteasomal inhibition	(Lin et al., 2016)
Berberine	Plant product	Reverses TDP-25 accumulation	(Chang et al., 2016)
Rapamycin	Small molecule	Clears TDP-25 and TDP-35 through autophagy	(Wang et al., 2012b)
LEVD-fmk	Small molecule	Inhibits Caspase 4 and reduces TDP-43 truncation	(Yin et al., 2019)
HSPB8 overexpression	Chaperone	Reduces TDP-25 levels in motor neurons as well as in myocytes through autophagy	(Cicardi et al., 2018) (Crippa et al., 2016)
KPT-335	Small molecule	Suppresses CTF-linked toxicity through inhibition of the Xpo1/Crm1 nuclear export pathway	(Chou et al., 2018)