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academies
August 16-17, 2018 | Copenhagen, Denmark
Dementia and Alzheimer ’s Disease
10
th
World congress on
Journal of Neurology and Neurorehabilitation Research | Volume: 3
Interactions of mitochondrial matrix proteins 17β-hydroxysteroid dehydrogenase type 10 and
cyclophilin D in people with Alzheimer disease and multiple sclerosis
Zdenka Kristofikova, Hofmannova A, Hromadkova L
and
Bartos A
National Institute of Mental Health, Czech Republic
T
he nucleus-encoded mitochondrial matrix protein
17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10)
operates via multiple enzymatic as well as non-enzymatic
functions. Its overexpression or deficiency is associated
with various pathologies. Increased levels of 17β-HSD10
in cerebrospinal fluid (reflecting probably its brain
overexpression)werefoundinpatientswithAlzheimerdisease
(AD) or multiple sclerosis (MS). Both neurodegenerative
diseases are accompanied by mitochondrial dysfunction.
Cytosolic 17β-HSD10 is imported into the mitochondrial
matrix via PINK1-Parkin-TOM/TIM pathway. Here, it binds to
cyclophilin D (cypD) and, by preventing its translocation to
the inner mitochondrial membrane, can regulate the opening
of the mitochondrial permeability transition pore mediated
by cypD. Under conditions of increased accumulation of
mitochondrial amyloid β (Aβ), observed especially in AD,
interactions of 17β-HSD10 and cypD could be eliminated
which may lead to apoptosis and mitochondrial dysfunction.
Using cerebrospinal fluid samples of people with AD or
MS and mitochondria isolated from double transgenic
McGill-R-Thy1-APP rats (one of the best animal models of
AD with intracelular accumulation of Aβ), we estimated
levels of 17β-HSD10, cypD, Aβ 1-42, total Aβ and of various
complexes (17β-HSD10 – Parkin, 17β-HSD10 – total Aβ,
17β-HSD10 – cypD). In AD, our results indicate that up-
regulation of 17β-HSD10 does not have to be followed by
increased levels in mitochondrial matrix and that the ability
of the protein to regulate cypD is weakened. In MS, on the
contrary, it seems that up-regulation can lead to increased
PINK1-Parkin-TOM/TIM transport and that 17β-HSD10
in mitochondrial matrix is fully functional. Supported by
GA CR (P304-12-G069) and AZV CR (16-27611A) projects.
Speaker Biography
Zdenka Kristofikova studied at Czech Technical Univerzity in Prague (Ing.,
Department of Nuclear Chemistry) and at Univerzity of Defence, Faculty of
Military Health Sciences in Hradec Kralove (PhD, Department of Toxicology), both
in the Czech Republic. She works at National Institute of Mental Health as a senior
researcher and a head of working group. She is interested in Alzheimer disease
for a long time (Web of Sciences: 122 results, 594 sum of times cited, h-index 15).
e:
zdenka.kristofikova@nudz.cz