ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 73 citations in OpenAlex.
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- Aging, Parkinson's Disease, and Models: What Are the Challenges?Aging biology · 2023Article
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- PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis.Protein & cell · 2022Article
- Brain Region- and Age-Dependent 5-Hydroxymethylcytosine Activity in the Non-Human Primate.Frontiers in aging neuroscience · 2022Article
- Astrocytes in Neurodegeneration: Inspiration From Genetics.Frontiers in neuroscience · 2022Review
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- Genetically modified large animal models for investigating neurodegenerative diseases.Cell & bioscience · 2021Review
- Co-editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype.Neuroscience bulletin · 2021Article
- Adeno-Associated Viral Vectors as Versatile Tools for Parkinson's Research, Both for Disease Modeling Purposes and for Therapeutic Uses.International journal of molecular sciences · 2021Review
- A New Rise of Non-Human Primate Models of Synucleinopathies.Biomedicines · 2021Review
- Comprehensive Perspectives on Experimental Models for Parkinson's Disease.Aging and disease · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2-3, 7-8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.