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. 2021 Aug;16(8):1550-1551.
doi: 10.4103/1673-5374.300987.

Therapeutic potential of alpha 5 subunit containing GABAA receptors in Alzheimer's disease

Andrea Kwakowsky  1 , Henry J Waldvogel  1 , Richard L M Faull  1
Affiliations

Therapeutic potential of alpha 5 subunit containing GABAA receptors in Alzheimer's disease

Andrea Kwakowsky et al. Neural Regen Res. 2021 Aug.
No abstract available

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Conflict of interest statement

None

Figures

Figure 1
Figure 1
α5IA restores Aβ1–42-induced increase in ambient GABA levels, upregulation of α5GABAAR expression, and increase in tonic inhibitory conductance. The extra-synaptic high affinity α5GABAARs can be persistently activated by low concentrations of ambient GABA to generate tonic inhibition, which is important for learning and memory. Aβ1–42-induced increase in ambient GABA and upregulation of α5GABAAR expression could result in increased activation of α5GABAARs, leading to increased tonic inhibition, ultimately disrupting the excitatory/inhibitory balance, leading to network dysfunction and causing cell death which potentially contribute to the observed cognitive decline in Alzheimer’s disease. α5GABAARs are potential drug targets for the treatment of the disease. The inverse agonist α5IA acting through these receptors decreases Aβ1–42-induced increase in tonic inhibition, restores ambient GABA levels, and expression of α5GABAARs. Aβ: Amyloid-β; APP: amyloid precursor protein; α5IA: 3-(5-methylisoxazol-3-yl)-6-[(1-methyl-1,2,3-triazol-4-yl)methyloxy]-1,2,4-triazolo,3,4–a]phthalazine; GABA: gamma-aminobutyric acid; GABAAR: GABA type A receptor; GAD: glut amic acid decarboxylase; Glu: glutamate.
See this image and copyright information in PMC

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