Jul 23, 2015

Sex hormone-related neurosteroids differentially rescue bioenergetic deficits induced by amyloid-β or hyperphosphorylated tau protein

Cellular and Molecular Life Sciences : CMLS
Amandine GrimmAnne Eckert

Abstract

Alzheimer's disease (AD) is an age-related neurodegenerative disease marked by a progressive cognitive decline. Metabolic impairments are common hallmarks of AD, and amyloid-β (Aβ) peptide and hyperphosphorylated tau protein--the two foremost histopathological signs of AD--have been implicated in mitochondrial dysfunction. Neurosteroids have recently shown promise in alleviating cognitive and neuronal sequelae of AD. The present study evaluates the impact of neurosteroids belonging to the sex hormone family (progesterone, estradiol, estrone, testosterone, 3α-androstanediol) on mitochondrial dysfunction in cellular models of AD: human neuroblastoma cells (SH-SY5Y) stably transfected with constructs encoding (1) the human amyloid precursor protein (APP) resulting in overexpression of APP and Aβ, (2) wild-type tau (wtTau), and (3) mutant tau (P301L), that induces abnormal tau hyperphosphorylation. We show that while APP and P301L cells both display a drop in ATP levels, they present distinct mitochondrial impairments with regard to their bioenergetic profiles. The P301L cells presented a decreased maximal respiration and spare respiratory capacity, while APP cells exhibited, in addition, a decrease in basal respiration, ATP turnov...Continue Reading

Mentioned in this Paper

Metabolic Process, Cellular
Study
Familial Alzheimer Disease (FAD)
Testosterone Measurement
Tauopathies
Progesterone and estrogen
Estrone Measurement
Transfection
Central Neuroblastoma
APP protein, human

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