Analysis of age-related changes in psychosine metabolism in the human brain
| Autor: | Benas Jakubauskas, Michael S. Marshall, Zane Hauck, Lisa DiAntonio, Richard B. van Breemen, Wil Bogue, Monika Stoskute, Ernesto R. Bongarzone, Emily A. Rue, Matthew Nichols, Carlos A. Saavedra-Matiz, Jeffrey H. Kordower |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Central Nervous System 0301 basic medicine Aging Heredity lcsh:Medicine Alzheimer's Disease Nervous System Cohort Studies 0302 clinical medicine Medicine and Health Sciences Aging brain lcsh:Science Aged 80 and over Brain Diseases Movement Disorders Multidisciplinary Mental Disorders Brain Parkinson Disease Neurodegenerative Diseases Human brain Middle Aged 3. Good health Substantia Nigra medicine.anatomical_structure Neurology Cerebral cortex alpha-Synuclein Female Autopsy Anatomy Galactosylceramidase Research Article Adult medicine.medical_specialty Central nervous system Substantia nigra Context (language use) White matter 03 medical and health sciences Alzheimer Disease Internal medicine Mental Health and Psychiatry Genetics medicine Humans Aged business.industry lcsh:R Psychosine Biology and Life Sciences 030104 developmental biology Endocrinology Mutation Dementia lcsh:Q business 030217 neurology & neurosurgery |
| Zdroj: | PLoS ONE, Vol 13, Iss 2, p e0193438 (2018) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0193438 |
| Popis: | α-Synuclein aggregation has been linked to Gaucher’s disease (GD) and Krabbe’s disease (KD), lysosomal conditions affecting glycosphingolipid metabolism. α-Synuclein pathology has been directly attributed to the dysregulation of glycosphingolipids in both conditions, specifically to increased galactosylsphingosine (psychosine) content in the context of KD. Furthermore, the gene (GALC) coding for the psychosine degrading enzyme galactosylceramidase (GALC), has recently been identified as a risk loci for Parkinson’s disease. However, it is unknown if changes in psychosine metabolism and GALC activity in the context of the aging human brain correlate with Parkinson’s disease. We investigated psychosine accumulation and GALC activity in the aging brain using fresh frozen post-mortem tissue from Parkinson’s (PD, n = 10), Alzheimer’s (AD, n = 10), and healthy control patients (n = 9), along with tissue from neuropsychiatric patients (schizophrenia, bipolar disorder and depression, n = 15 each). An expanded mutational analysis of PD (n = 20), AD (n = 10), and healthy controls (n = 30) examined if PD was correlated with carriers for severe GALC mutations. Psychosine content within the cerebral cortex of PD patients was elevated above control patients. Within all patients, psychosine displayed a significant (p |
| Databáze: | OpenAIRE |
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