Ursodeoxycholic Acid Improves Mitochondrial Function and Redistributes Drp1 in Fibroblasts from Patients with Either Sporadic or Familial Alzheimer's Disease

Journal of Molecular Biology
Simon M BellHeather Mortiboys

Abstract

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Mitochondrial abnormalities have been identified in many cell types in AD, with deficits preceding the development of the classical pathological aggregations. Ursodeoxycholic acid (UDCA), a treatment for primary biliary cirrhosis, improves mitochondrial function in fibroblasts derived from Parkinson's disease patients as well as several animal models of AD and Parkinson's disease. In this paper, we investigated both mitochondrial function and morphology in fibroblasts from patients with both sporadic and familial AD. We show that both sporadic AD (sAD) and PSEN1 fibroblasts share the same impairment of mitochondrial membrane potential and alterations in mitochondrial morphology. Mitochondrial respiration, however, was decreased in sAD fibroblasts and increased in PSEN1 fibroblasts. Morphological changes seen in AD fibroblasts include reduced mitochondrial number and increased mitochondrial clustering around the cell nucleus as well as an increased number of long mitochondria. We show here for the first time in AD patient tissue that treatment with UDCA increases mitochondrial membrane potential and respiration as well as reducing the amount of long mitochondri...Continue Reading

Citations

Jun 19, 2019·Biomolecules·Yoshimitsu Kiriyama, Hiromi Nochi
Sep 12, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Stephen J KeelyNatalia K Lajczak-McGinley
Aug 23, 2020·International Journal of Molecular Sciences·Stephanie M Grant, Sharon DeMorrow
May 30, 2020·International Journal of Molecular Sciences·Serena StangaAlessandro Vercelli
Dec 2, 2020·International Journal of Molecular Sciences·Simon M BellHeather Mortiboys
Jan 21, 2021·Frontiers in Cell and Developmental Biology·Jannik PrasuhnKishore R Kumar
Jan 13, 2021·Neural Regeneration Research·Isaac G OnyangoGorazd B Stokin
Jan 15, 2021·Biomedicines·Simon M BellHeather Mortiboys
Apr 9, 2021·Frontiers in Cell and Developmental Biology·Kai-Lieh LinTsu-Kung Lin

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Datasets Mentioned

BETA
GM07376
ND34730
GM23967

Methods Mentioned

BETA
biopsy
sumoylation
Assay
PCR

Software Mentioned

Harmony
Seahorse Analyser
InCell Developer
GeneSnap
GraphPad Prism

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