TABLE 1.

Drugs identified for AD treatment in zebrafish models.

Compound	Classification	Model	Effects on phenotype	Behavioral method	Molecular mechanism	References
Surfen and oxalyl surfen	Heparan sulfate antagonist	Tau-P301L-Tg	Rescue impaired escape response; Rescue motor neuron defects	Touch-evoked escape response, 48 hpf	Decrease p-tau	Naini et al. (2018)
AR-534	GSK-3β inhibitor	Tau-P301L-Tg	Not applicable	Touch-evoked escape response, 48 hpf	Decrease p-tau	Paquet et al. (2009)
Linarin	Flavonoid glycoside	AlCl3	Protect against dyskinesia	Light-dark test, 3 dpf	Inhibit AChE activity	Pan et al. (2019)
TDZD-8	GSK-3β inhibitor	OKA	Reduce mortality rate; Reverse cognitive deficits	Spatial discrimination test, 12–15 months	Decrease p-tau, PP2A and the ratio of active: Inactive GSK3β	Koehler et al. (2019)
LKE	Lanthionine ketimine derivatives	OKA	Reverse cognitive defects; Resist cell apoptosis	Spatial discrimination test, 12–15 months	Increase BDNF, pPKB/Akt and pCREB	Koehler et al. (2018)
Li2CO3	GSK-3β inhibitor	Scopolamine	Reverse cognitive deficits	Novel tank test, fish; Y-maze task, 6 months	Decrease p-tau	Zanandrea et al. (2018)
Compound 4m	3-Arylcoumarin derivatives	AlCl3	Alleviated behavior symptoms	Locomotion test with trajectory recording; 72 hpf	Inhibit AChE and BuChE activity	Hu et al. (2019)
LiCl	GSK-3β inhibitor	Aβ42 injection; Tau-P301L-Tg	Reverse cognitive deficits	Avoidance learning; touch-evoked escape response, 5 dpf	Decrease p-tau	Nery et al. (2014)
Cotinine/6-hydroxy-l-nicotine	Nicotine derivate	Scopolamine	Rescue anxiety-like behavior and memory impairment	Novel tank test, 15–16 days; Y-maze task, 17–18 days; Object discrimination test, 19–23 days	Reduce oxidative stress and AChE activity; upregulate npy, egr1, bdnf, nrf2a mRNA levels	Boiangiu et al. (2021)
TEO	Thymus vulgaris L	Scopolamine	Reduce amnesia and anxiety	Novel tank test, 7 days; Y-maze task, 8 days; Object discrimination test, 9–13 days	Reduce AChE activity and brain antioxidant capacity	Capatina et al. (2020)
LDC8	CDK5 inhibitor	Aβ injection	Reduce neurodegeneration, neuroinflammation and protect synapses	Not applicable	Decrease p-tau; inhibit GSK3β and CDK5	Reinhardt et al. (2019)
TM-10	Ferulic acid derivatives	AlCl3; Aβ injection	Improve response efficiency and exercise capacity; prevent memory loss	Light-dark test, 3 dpf	Inhibit BuChE, MAO activity; Disaggregate Aβ	Sang et al. (2019)
Compound 4e	Cinnamic acid hybrids derivates	AlCl3	Improve dyskinesia recovery rate and reaction capacity	Locomotion test, 2 dpf	Inhibit Aβ42 accumulation, reverse BuChE activity, inhibit MAO-B activity	Wang et al. (2021)
βCas AuNPs	Nanoparticles	Aβ injection	Rescue motility and cognitive dysfunction	Swimming behavior with response to tap stimuli, 5 dpf	Eliminate amyloid plaque formation; reduce ROS; recover synaptophysin	Javed et al. (2019)
CQDs	Nanostructures	IAPP and Aβ microinjection	Rescue impaired zebrafish embryonic hatching	Not applicable	Suppress ROS production, deactivate BACE1	Han et al. (2017)