Table 2 Summary of AD-related effects of Rho GTPase pharmacological inhibition

Rac1

NSC23766, 6-MP, EHT1864

• Hippocampal neurons from 15-day-old embryonic ICR mice

• HEK293, RACT17N (negative mutant), and siRNA

Decreased APP protein and mRNA levels.

[22]

• SN4741 cells

• Primary neuron cultures from the cortical lobes of E18 Sprague–Dawley rat embryos, hippocampal and entorhinal

Blocked Aβ₄₂-associcated neuronal death.

[25]

• SH-SY5Y, HEK293-swAPP, and HEK293-BACE cells

Decreased Aβ protein level. Did not affect BACE, α-secretase, and Notch1. Inhibited γ-secretase, indirectly.

[52]

NSAIDs

Ibuprofen, cicoflenac, indomethacin, fenoprofen, sulindac sulfide, meclofen, flurbiprofen

• SH-SY5Y-swAPP

• PDAPP mice

Decreased Aβ₄₂ production.

[53]

• CHO WT-APP and PS1-M146L.

• HS683-swAPP and PSN

• 3-month-old Tg2576

Decreased Aβ₄₂ formation and increased Aβ₃₈. Acute dosing in mice decreased Aβ₄₂ brain levels

[54]

• 10-month-old Tg2576

Reduced CNS inflammatory response and amyloid plaque pathology.

[55]

• Neuro2a N2a NL/N-swAPP and NotchΔE

Decreased Aβ₄₂, no effect on Aβ₄₀ and Notch1.

[62]

• H4-swAPP

• CHO-sw/loAPP

• 3-month-old female Tg2576 mice

Decreased Aβ42 in a γ-secretase-dependent manner both in vitro and in vivo.

[63]

Indomethacin

• Mild/moderate AD patients

Slight improvement in cognitive tests: Mini-Mental State Examination, Alzheimer's Disease Assessment Scale, Boston Naming Test, and Token Test.

[56]

R-Flurbiprofen

• Mild AD patients

Ineffective at preventing/delaying loss of cognition or function.

[64]

RhoA/ROCK

Y27632, SR3677, HA-1077

• CHO with both wild-type (WT) human APP751 and human mutant PS1.

Inhibited Aβ₄₂ production.

[67]

• Platelets

Inhibited cytoskeletal reorganization following activation with Aβ_25–35.

[30]

• SH-SY5Y cells

• ~2-month-old PDAPP

Lowered Aβ₄₂ levels in vitro and in vivo.

[53]

• SH-SY5Y, HEK293, and primary cortical neurons from embryonic day 17 mouse embryos

• 3-month-old 5 × FAD

Inhibited BACE activity and Aβ production.

[68]