Research breakthrough opens doors for Parkinson's Disease Treatment

2023-11-06

In a new article in Nature Communications, researchers at Uppsala University and KI identify prosaposin as a possible target for drugs and treatment against Parkinson's disease. "Our results open the doors to an exciting future for research in our field," states Per Andrén and Ibrahim Kaya at Uppsala University’s Faculty of Pharmacy.

Per Andrén, Professor of Mass Spectrometry Imaging
Per Andrén, Professor of Mass Spectrometry Imaging

New research at Uppsala University and the Karolinska Institute reveals that increased levels of prosaposin (PSAP) – a protein influencing lipid metabolism – can counteract Parkinson's disease. Analyzing blood plasma and cerebrospinal fluid from patients with Parkinson's disease, the researchers found altered levels of PSAP, which in turn correlated with the patients' motor impairments. Via mouse models, the researchers further noted that a deficiency of PSAP leads to behavioral changes and a reconfiguration of lipid metabolism in the brain.

“We also found altered PSAP levels in post-mortem brains from Parkinson's patients and can link variants of the protein to Parkinson's disease. Thus, our results identify PSAP as a potential target for the development of new drugs and the treatment of Parkinson's disease, which opens the doors to an exciting future for research in our field, states Per Andrén, Professor of Mass Spectrometry Imaging at Uppsala University's Faculty of Pharmacy.

The study was carried out in collaboration between Per Andren and Ibrahim Kaya at Uppsala University and Per Svenningsson's research group at Karolinska Institutet's Department of Clinical Neuroscience. The results are published in Nature Communications.

FACTS

  • Using transgenic mouse models, the researchers found that dopaminergic PSAP-deficient mice display behavioral anomalies including hypolocomotion and depression/anxiety-like symptoms.
  • Spatial lipidomics using MALDI-Fourier-transform ion cyclotron resonance MSI revealed an accumulation of highly unsaturated and shortened glycerophospholipids and reduction of sphingolipids throughout the brains of these mice.
  • Overexpression of PSAP via AAV and encapsulated cell biodelivery protected against 6-OHDA and α-synuclein toxicity in wild-type rodents.
  • These findings suggest PSAP may maintain dopaminergic lipid homeostasis, which is dysregulated in Parkinson's disease, and counteract experimental parkinsonism.

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CONTACT

KONTAKTa Per AndrénPer Andrén, Professor
Dep. of Pharmaceutical Biosciences
per.andren@farmbio.uu.se

Ibrahim Kaya, forskareIbrahim Kaya, Researcher
Dep. of Pharmaceutical Biosciences
Ibrahim.Kaya@uu.se

text, Magnus Alsne, photo: Mikael Wallerstedt, private

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Last modified: 2022-11-08