Table 3.

Potential therapeutic targets for the treatment of tauopathies.

Signaling Targets	Therapeutics	Settings/Organisms	Outcomes/Affected Functional Effects	Affected Phosphorylated Sites	State of Process	Reference
Interfering HSPG-tau interaction	HS oligosaccharide containing two 3-O-sulfo group	Mouse lung endothelial cells (MLECs)	Blocking tau cell surface binding and internalization	NA	Research stage	[41]
Intervening the formation of NLRP3 inflammasome	Cias1 and Pycard gene dysfunction	FTD mice model, ACS- or NLRP3 -deficient Tau22 mice	Attenuating the level of tau hyperphosphorylation (AT8) in hippocampus Decreasing level of GSK-3β and CaMKII-α activities	pS416	Research stage	[59,87]
Hsp90 cochaperones, Aha1	KU-177	Inducible HEK-P301L cells transfected with Aha1	Reduced insoluble tau	pS396/404	Research stage	[111]
Promoting the autophagy-lysosomal pathway (ALP)	Curcumin analog C1	Transgenic mice models, 5×FAD, P301S, and 3×Tg	Attenuating both APP and tau pathology Activating autophagy-lysosomal pathway (ALP)	pS396/404 pS202/T205	Research stage	[56]
Promoting CX3CL1 regulated signaling	CX3CL1 overexpression	P19 tau pathology mice model	Reducing neurodegeneration and improving cognitive function with increased neurogenesis	NA	Research stage	[112]
Inhibiting extra-synaptic NMDA receptor	RL-208	A mice model of late-onset AD (LOAD)	Reduced apoptosis-related proteins, caspase-3 and calpain-1 Increased phosphorylation level of NMDA2B Decreased kinase activity of Cdk5/p25 accompanied by a reduced level of p-tau	pS396	Research stage	[114]
GLT1 upregulation	LDN/OSU-0212320	Neuron and astrocyte coculture	Upregulating the expression of EAAT2 in primary astrocytes Preventing neurons from glutamate-induced cytotoxicity in a neuronal-astrocytic coculture	NA	Research stage	[116]
ApoE4 gene therapy	AAV ApoE2-expressing vector targeting CNS/CSF ApoE4	AD patients	Targeting to transform ApoE4 in CNS/CSF of AD patients into ApoE2, which is less toxic	NA	Phase I	[117]