ArticleJournal of Parkinson's disease2021
Effects of Alpha-Synuclein Targeted Antisense Oligonucleotides on Lewy Body-Like Pathology and Behavioral Disturbances Induced by Injections of Pre-Formed Fibrils in the Mouse Motor Cortex.
Article in Journal of Parkinson's disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 26 citations in OpenAlex.
- An acute dose of glyphosate alters novel object exploration and hippocampal cFos expression in a sex-dependent manner in wildtype mice.Neuroscience · 2026Article
- Multiple system atrophy: advances in pathogenesis and emerging therapeutic strategies.Journal of neurology · 2025Review
- Behavioral disorders in dementia with Lewy bodies: old and new knowledge.Journal of neural transmission (Vienna, Austria : 1996) · 2025Review
- Intrastriatal injection of alpha-synuclein preformed fibrils to rats results in L-DOPA reversible sensorimotor impairments and alterations in non-motor function.Frontiers in neuroscience · 2025Article
- Effects of local reduction of endogenous α-synuclein using antisense oligonucleotides on the fibril-induced propagation of pathology through the neural network in wild-type mice.Acta neuropathologica communications · 2024Article
- Recent Advances in Clinical Trials in Multiple System Atrophy.Current neurology and neuroscience reports · 2024Review
- Cognitive dysfunction in animal models of human lewy-body dementia.Frontiers in aging neuroscience · 2024Review
- Cortical Lewy body injections induce long-distance pathogenic alterations in the non-human primate brain.NPJ Parkinson's disease · 2023Article
- Anxiety in synucleinopathies: neuronal circuitry, underlying pathomechanisms and current therapeutic strategies.NPJ Parkinson's disease · 2023Review
- SNCA genetic lowering reveals differential cognitive function of alpha-synuclein dependent on sex.Acta neuropathologica communications · 2022Article
- Synucleinopathy in Amyotrophic Lateral Sclerosis: A Potential Avenue for Antisense Therapeutics?International journal of molecular sciences · 2022Review
- Infusion of etoposide in the CA1 disrupts hippocampal immediate early gene expression and hippocampus-dependent learning.Scientific reports · 2022Article
- miRNA and antisense oligonucleotide-based α-synuclein targeting as disease-modifying therapeutics in Parkinson's disease.Frontiers in pharmacology · 2022Review
- Alpha-Synuclein and Cognitive Decline in Parkinson Disease.Life (Basel, Switzerland) · 2021Review
- Viral alpha-synuclein knockdown prevents spreading synucleinopathy.Brain communications · 2021Article
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3 authors at 2 institutions in 1 country.
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Abstract
backgroundAlpha-synuclein (αsyn) characterizes neurodegenerative diseases known as synucleinopathies. The phosphorylated form (psyn) is the primary component of protein aggregates known as Lewy bodies (LBs), which are the hallmark of diseases such as Parkinson's disease (PD). Synucleinopathies might spread in a prion-like fashion, leading to a progressive emergence of symptoms over time. αsyn pre-formed fibrils (PFFs) induce LB-like pathology in wild-type (WT) mice, but questions remain about their progressive spread and their associated effects on behavioral performance.
objectiveTo characterize the behavioral, cognitive, and pathological long-term effects of LB-like pathology induced after bilateral motor cortex PFF injection in WT mice and to assess the ability of mouse αsyn-targeted antisense oligonucleotides (ASOs) to ameliorate those effects.
methodsWe induced LB-like pathology in the motor cortex and connected brain regions of male WT mice using PFFs. Three months post-PFF injection (mpi), we assessed behavioral and cognitive performance. We then delivered a targeted ASO via the ventricle and assessed behavioral and cognitive performance 5 weeks later, followed by pathological analysis.
resultsAt 3 and 6 mpi, PFF-injected mice showed mild, progressive behavioral deficits. The ASO reduced total αsyn and psyn protein levels, and LB-like pathology, but was also associated with some deleterious off-target effects not involving lowering of αsyn, such as a decline in body weight and impairments in motor function.
conclusionsThese results increase understanding of the progressive nature of the PFF model and support the therapeutic potential of ASOs, though more investigation into effects of ASO-mediated reduction in αsyn on brain function is needed.
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