ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Leucine-rich repeat kinase 2 modulates neuroinflammation and neurotoxicity in models of human immunodeficiency virus 1-associated neurocognitive disorders.
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. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Dysregulation of Immune Mediators and Synaptic Plasticity in Central Nervous System Disorders.Cells · 2026Review
- LRRK2 kinase activity restricts NRF2-dependent mitochondrial protection in microglia.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
- Infectious Diseases.Advances in neurobiology · 2024Review
- Article
- Perspective on the current state of the LRRK2 field.NPJ Parkinson's disease · 2023Review
- Targeting Human Proteins for Antiviral Drug Discovery and Repurposing Efforts: A Focus on Protein Kinases.Viruses · 2023Review
- LRRK2 Kinase Inhibition Attenuates Astrocytic Activation in Response to Amyloid βBiomolecules · 2023Article
- Regulation of α-synuclein homeostasis and inflammasome activation by microglial autophagy.Science advances · 2022Review
- Neuroinflammation represents a common theme amongst genetic and environmental risk factors for Alzheimer and Parkinson diseases.Journal of neuroinflammation · 2022Review
- URMC-099 prophylaxis prevents hippocampal vascular vulnerability and synaptic damage in an orthopedic model of delirium superimposed on dementia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Effect of LRRK2 protein and activity on stimulated cytokines in human monocytes and macrophages.NPJ Parkinson's disease · 2022Article
- The Role of Pathogens and Anti-Infective Agents in Parkinson's Disease, from Etiology to Therapeutic Implications.Journal of Parkinson's disease · 2022Review
- Viral infections and their relationship to neurological disorders.Archives of virology · 2021Review
- Dissecting the non-neuronal cell contribution to Parkinson's disease pathogenesis using induced pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2021Review
- Genetic Imaging of Neuroinflammation in Parkinson's Disease: Recent Advancements.Frontiers in cell and developmental biology · 2021Review
- Neuron-autonomous susceptibility to induced synuclein aggregation is exacerbated by endogenousBrain communications · 2020Article
- Article
- Multiple-Hit Hypothesis in Parkinson's Disease: LRRK2 and Inflammation.Frontiers in neuroscience · 2020Review
- Inhibitory Control Deficits Associated with Upregulation of CBJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Leucine-rich repeat kinase 2 (LRRK2) is the single most common genetic cause of both familial and sporadic Parkinson's disease (PD), both of which share pathogenetic and neurologic similarities with human immunodeficiency virus 1 (HIV-1)-associated neurocognitive disorders (HAND). Pathologic LRRK2 activity may also contribute to neuroinflammation, because microglia lacking LRRK2 exposed to proinflammatory stimuli have attenuated responses. Because microglial activation is a hallmark of HIV-1 neuropathology, we have investigated the role of LRRK2 activation using in vitro and in vivo models of HAND. We hypothesize that LRRK2 is a key modulator of microglial inflammatory responses, which play a pathogenic role in both HAND and PD, and that these responses may cause or exacerbate neuronal damage in these diseases. The HIV-1 Tat protein is a potent neurotoxin produced during HAND that induces activation of primary microglia in culture and long-lasting neuroinflammation and neurotoxicity when injected into the CNS of mice. We found that LRRK2 inhibition attenuates Tat-induced pS935-LRRK2 expression, proinflammatory cytokine and chemokine expression, and phosphorylated p38 and Jun N-terminal kinase signaling in primary microglia. In our murine model, cortical Tat injection in LRRK2 knock-out (KO) mice results in significantly diminished neuronal damage, as assessed by microtubule-associated protein 2 (MAP2), class III β-tubulin TUJ1, synapsin-1, VGluT, and cleaved caspase-3 immunostaining. Furthermore, Tat-injected LRRK2 KO animals have decreased infiltration of peripheral neutrophils, and the morphology of microglia from these mice were similar to that of vehicle-injected controls. We conclude that pathologic activation of LRRK2 regulates a significant component of the neuroinflammation associated with HAND.
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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.