ArticleNeurotoxicity research2018
Differential Alterations in Metabolism and Proteolysis-Related Proteins in Human Parkinson's Disease Substantia Nigra.
Article in Neurotoxicity research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Cortisol levels, motor, cognitive and behavioral symptoms in Parkinson's disease: a systematic review.Journal of neural transmission (Vienna, Austria : 1996) · 2019Pooled it
- The lifespan continuum of brain disorders: investigating links between neurodevelopmental and neurodegenerative disease-chicken or egg?Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Autism patient-derived SHANK2BMolecular psychiatry · 2024Article
- Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.Neurotoxicology · 2024Review
- Disruption of Dopamine Homeostasis Associated with Alteration of Proteins in Synaptic Vesicles: A Putative Central Mechanism of Parkinson's Disease Pathogenesis.Aging and disease · 2024Review
- Single-neuron neurodegeneration as a degenerative model for Parkinson's disease.Neural regeneration research · 2024Review
- On the Role of Iron in Idiopathic Parkinson's Disease.Biomedicines · 2023Review
- Oxidative Stress and Neuroinflammation in Parkinson's Disease: The Role of Dopamine Oxidation Products.Antioxidants (Basel, Switzerland) · 2023Review
- A Preclinical Model for Parkinson's Disease Based on Transcriptional Gene Activation via KEAP1/NRF2 to Develop New Antioxidant Therapies.Antioxidants (Basel, Switzerland) · 2023Review
- Differential expression ofFrontiers in molecular neuroscience · 2023Article
- Treatment; Moussa B.H. Youdim.Journal of neural transmission (Vienna, Austria : 1996) · 2022Article
- Neuroprotection against Aminochrome Neurotoxicity: Glutathione Transferase M2-2 and DT-Diaphorase.Antioxidants (Basel, Switzerland) · 2022Review
- Identifying Potential Mitochondrial Proteome Signatures Associated with the Pathogenesis of Pulmonary Arterial Hypertension in the Rat Model.Oxidative medicine and cellular longevity · 2022Article
- Genomic Regions Associated with the Position and Number of Hair Whorls in Horses.Animals : an open access journal from MDPI · 2021Article
- Stable expression of the human dopamine transporter in N27 cells as an in vitro model for dopamine cell trafficking and metabolism.Toxicology in vitro : an international journal published in association with BIBRA · 2021Article
- The Catecholaldehyde Hypothesis for the Pathogenesis of Catecholaminergic Neurodegeneration: What We Know and What We Do Not Know.International journal of molecular sciences · 2021Review
- Mutant Presenilin 1 Dysregulates Exosomal Proteome Cargo Produced by Human-Induced Pluripotent Stem Cell Neurons.ACS omega · 2021Article
- Function and Regulation of ALDH1A1-Positive Nigrostriatal Dopaminergic Neurons in Motor Control and Parkinson's Disease.Frontiers in neural circuits · 2021Review
- Diverse midbrain dopaminergic neuron subtypes and implications for complex clinical symptoms of Parkinson's disease.Ageing and neurodegenerative diseases · 2021Article
- Modeling Parkinson's Disease: Not Only Rodents?Frontiers in aging neuroscience · 2021Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease is the most common neurodegenerative disorder after Alzheimer's disease, with the majority of cases being sporadic or "idiopathic". The aetiology of the sporadic form is still unknown, but there is a broad consensus that Parkinson's disease involves multiple pathways. In previous human post-mortem studies investigating substantia nigra of parkinsonian subjects, gene expression alterations in various metabolic pathways including protein folding, trafficking, aggregation, ubiquitination and oxidative stress were found. These studies revealed transcriptomic dysregulation of various genes, amongst others Skp1A and PSMC4 (part of ubiquitin-proteasome system), HSC70 (belonging to the chaperone family) and ALDH1A1 (an enzyme involved in the catabolism of dopamine). To investigate whether these alterations are manifested at the protein level, we performed immunohistochemical analysis in the substantia nigra of Parkinson's disease and compared them to Alzheimer's disease and non-neurological post-mortem controls. We were able to confirm cell-specific reductions in the protein content of ALHD1A1 and Skp1A in the dopaminergic neurons of the substantia nigra of Parkinsonian patients compared to Alzheimer's and control subjects. Furthermore, we observed particular distribution for HSC70 and PSMC4 in the cytoplasm and accumulation within Lewy body in the dopaminergic neurons of the substantia nigra in Parkinson patients. These findings, together with previous evidence, suggest a malfunction of the ubiquitin-proteasome and possible autophagy systems as major players in protein misfolding and aggregation in Parkinson's disease. Nevertheless, this needs further proof, possibly with trajectory time line.
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