TY - JOUR

T1 - Loss of swiss cheese in neurons contributes to neurodegeneration with mitochondria abnormalities, reactive oxygen species acceleration and accumulation of lipid droplets in Drosophila brain

AU - Melentev, Pavel A.

AU - Ryabova, Elena V.

AU - Surina, Nina V.

AU - Zhmujdina, Darya R.

AU - Komissarov, Artem E.

AU - Ivanova, Ekaterina A.

AU - Boltneva, Natalia P.

AU - Makhaeva, Galina F.

AU - Sliusarenko, Mariana I.

AU - Yatsenko, Andriy S.

AU - Mohylyak, Iryna I.

AU - Matiytsiv, Nataliya P.

AU - Shcherbata, Halyna R.

AU - Sarantseva, Svetlana V.

N1 - Melentev, P.A.; Ryabova, E.V.; Surina, N.V.; Zhmujdina, D.R.; Komissarov, A.E.; Ivanova, E.A.; Boltneva, N.P.; Makhaeva, G.F.; Sliusarenko, M.I.; Yatsenko, A.S.; Mohylyak, I.I.; Matiytsiv, N.P.; Shcherbata, H.R.; Sarantseva, S.V. Loss of swiss cheese in Neurons Contributes to Neurodegeneration with Mitochondria Abnormalities, Reactive Oxygen Species Acceleration and Accumulation of Lipid Droplets in Drosophila Brain. Int. J. Mol. Sci. 2021, 22, 8275. https://doi.org/10.3390/ijms22158275

PY - 2021/8/1

Y1 - 2021/8/1

N2 - Various neurodegenerative disorders are associated with human NTE/PNPLA6 dysfunc-tion. Mechanisms of neuropathogenesis in these diseases are far from clearly elucidated. Hereditary spastic paraplegia belongs to a type of neurodegeneration associated with NTE/PNLPLA6 and is implicated in neuron death. In this study, we used Drosophila melanogaster to investigate the consequences of neuronal knockdown of swiss cheese (sws)—the evolutionarily conserved ortholog of human NTE/PNPLA6—in vivo. Adult flies with the knockdown show longevity decline, locomotor and memory deficits, severe neurodegeneration progression in the brain, reactive oxygen species level acceleration, mitochondria abnormalities and lipid droplet accumulation. Our results suggest that SWS/NTE/PNPLA6 dysfunction in neurons induces oxidative stress and lipid metabolism al-terations, involving mitochondria dynamics and lipid droplet turnover in neurodegeneration path-ogenesis. We propose that there is a complex mechanism in neurological diseases such as hereditary spastic paraplegia, which includes a stress reaction, engaging mitochondria, lipid droplets and en-doplasmic reticulum interplay.

AB - Various neurodegenerative disorders are associated with human NTE/PNPLA6 dysfunc-tion. Mechanisms of neuropathogenesis in these diseases are far from clearly elucidated. Hereditary spastic paraplegia belongs to a type of neurodegeneration associated with NTE/PNLPLA6 and is implicated in neuron death. In this study, we used Drosophila melanogaster to investigate the consequences of neuronal knockdown of swiss cheese (sws)—the evolutionarily conserved ortholog of human NTE/PNPLA6—in vivo. Adult flies with the knockdown show longevity decline, locomotor and memory deficits, severe neurodegeneration progression in the brain, reactive oxygen species level acceleration, mitochondria abnormalities and lipid droplet accumulation. Our results suggest that SWS/NTE/PNPLA6 dysfunction in neurons induces oxidative stress and lipid metabolism al-terations, involving mitochondria dynamics and lipid droplet turnover in neurodegeneration path-ogenesis. We propose that there is a complex mechanism in neurological diseases such as hereditary spastic paraplegia, which includes a stress reaction, engaging mitochondria, lipid droplets and en-doplasmic reticulum interplay.

KW - Drosophila melanogaster

KW - Hereditary spastic paraplegia

KW - Lipid droplets

KW - Mitochondria

KW - Neurodegeneration

KW - NTE

KW - Oxidative stress

KW - PNPLA6

KW - ROS

KW - Swiss cheese

UR - http://www.scopus.com/inward/record.url?scp=85111458976&partnerID=8YFLogxK

U2 - 10.3390/ijms22158275

DO - 10.3390/ijms22158275

M3 - Article

C2 - 34361042

AN - SCOPUS:85111458976

VL - 22

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 15

M1 - 8275

ER -