fig2

Deregulation of mitochondrial reverse electron transport alters the metabolism of reactive oxygen species and NAD<sup>+</sup>/NADH and presents a therapeutic target in Alzheimer's disease

Figure 2. In vivo efficacy of CPT in the 5xFAD mouse model of AD. (A and B) Measurements of NAD+/NADH ratio and H2O2 level in whole brain lysates (A) or purified mitochondria under in vitro RET and FET conditions (B) of wild-type control, and vehicle and CPT-treated 5xFAD mice; (C) Measurement of mitochondrial succinate level in non-transgenic wild-type control and 5xFAD mice treated with vehicle or CPT; (D) Measurements of clasping score in the hindlimb clasping assay on non-transgenic control and 5xFAD mice or 5xFAD mice treated with vehicle or CPT (50 mg/kg) by IP administration; (E) Immunostaining and data quantification of amyloid plaque load and number of microglia surrounding each plaque in the CA1 region of the hippocampus of vehicle or CPT-treated 5xFAD mouse brain; (F) Immunostaining and data quantification of C3-positive astrocytes in the CA1 region of the hippocampus of vehicle or CPT-treated 5xFAD mouse brain; **P < 0.01, ***P < 0.001 in Student’s t-test or one-way ANOVA test. CPT: CPT2008, 6-chloro-3-(2,4-dichloro-5-methoxyphenyl)-2-mecapto-7-methoxyquinazolin-4(3H)-one; FAD: familial Alzheimer’s disease; AD: Alzheimer’s disease.

Ageing and Neurodegenerative Diseases
ISSN 2769-5301 (Online)

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https://www.portico.org/publishers/oae/