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Prosaposin maintain...
Prosaposin maintains lipid homeostasis in dopamine neurons and counteracts experimental parkinsonism in rodents
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- He, Yachao (author)
- Karolinska Inst, Dept Clin Neurosci, Translat Neuropharmacol, Stockholm, Sweden.
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- Kaya, Ibrahim (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Shariatgorji, Reza (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Lundkvist, Johan (author)
- Karolinska Inst, Div Neurogeriatr, Dept Neurobiol, Care Sci & Soc, Stockholm, Sweden.;Sinfonia Biotherapeut AB, Huddinge, Sweden.
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- Wahlberg, Lars U. (author)
- Karolinska Inst, Div Neurogeriatr, Dept Neurobiol, Care Sci & Soc, Stockholm, Sweden.
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- Nilsson, Anna (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Mamula, Dejan (author)
- Karolinska Inst, Dept Clin Neurosci, Translat Neuropharmacol, Stockholm, Sweden.
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- Kehr, Jan (author)
- Karolinska Inst, Sect Pharmacol Neurochem, Dept Physiol & Pharmacol, Solna, Sweden.
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- Zareba-Paslawska, Justyna (author)
- Karolinska Inst, Dept Clin Neurosci, Translat Neuropharmacol, Stockholm, Sweden.
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- Biverstal, Henrik (author)
- Karolinska Institutet,Sinfonia Biotherapeut AB, Huddinge, Sweden.;Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden.
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- Chergui, Karima (author)
- Karolinska Institutet,Karolinska Inst, Dept Physiol & Pharmacol, Lab Mol Neurophysiol, Stockholm, Sweden.
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- Zhang, Xiaoqun (author)
- Karolinska Inst, Dept Clin Neurosci, Translat Neuropharmacol, Stockholm, Sweden.
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- Andrén, Per E., Professor, 1957- (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Svenningsson, Per (author)
- Karolinska Inst, Dept Clin Neurosci, Translat Neuropharmacol, Stockholm, Sweden.;Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, London, England.
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Karolinska Inst, Dept Clin Neurosci, Translat Neuropharmacol, Stockholm, Sweden Institutionen för farmaceutisk biovetenskap (creator_code:org_t)
- Springer Nature, 2023
- 2023
- English.
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Abstract
Subject headings
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- Prosaposin (PSAP) modulates glycosphingolipid metabolism and variants have been linked to Parkinson's disease (PD). Here, we find altered PSAP levels in the plasma, CSF and post-mortem brain of PD patients. Altered plasma and CSF PSAP levels correlatewith PD-relatedmotor impairments. Dopaminergic PSAP-deficient (cPSAP(DAT)) mice display hypolocomotion and depression/anxiety-like symptoms with mildly impaired dopaminergic neurotransmission, while serotonergic PSAP-deficient (cPSAP(SERT)) mice behave normally. Spatial lipidomics revealed an accumulation of highly unsaturated and shortened lipids and reduction of sphingolipids throughout the brains of cPSAP(DAT) mice. The overexpression of alpha-synuclein via AAV lead to more severe dopaminergic degeneration and higher p-Ser129 alpha-synuclein levels in cPSAP(DAT) mice compared to WT mice. Overexpression of PSAP via AAV and encapsulated cell biodelivery protected against 6-OHDA and alpha-synuclein toxicity in wild-type rodents. Thus, these findings suggest PSAP may maintain dopaminergic lipid homeostasis, which is dysregulated in PD, and counteract experimental parkinsonism.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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He, Yachao
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Kaya, Ibrahim
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Shariatgorji, Re ...
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Lundkvist, Johan
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Wahlberg, Lars U ...
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Nilsson, Anna
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Mamula, Dejan
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Kehr, Jan
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Zareba-Paslawska ...
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Biverstal, Henri ...
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Chergui, Karima
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Zhang, Xiaoqun
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Andrén, Per E., ...
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Svenningsson, Pe ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Nature Communica ...
- By the university
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Uppsala University
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Karolinska Institutet