ArticleCellular logistics2012
PAK in Alzheimer disease, Huntington disease and X-linked mental retardation.
Article in Cellular logistics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 86 citations in OpenAlex.
- PAK1 (p21-Activated Kinase 1) and Its Role in Neurodevelopmental Disorders-New Case Report and a Comprehensive Review.International journal of molecular sciences · 2025Review
- PAK1 inhibitor NVS-PAK1-1 preserves dendritic spines in amyloid/tau exposed neurons and 5xFAD mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Restoring endogenous Dlg4/PSD95 expression by an artificial transcription factor ameliorates cognitive and motor learning deficits in the R6/2 mouse model of Huntington's disease.Clinical epigenetics · 2025Article
- Role of LIMK1-cofilin-actin axis in dendritic spine dynamics in Alzheimer's disease.Cell death & disease · 2025Review
- Genetic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats.Genes, brain, and behavior · 2025Article
- Genomic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats.bioRxiv : the preprint server for biology · 2024Article
- Article
- The molecular basis of p21-activated kinase-associated neurodevelopmental disorders: From genotype to phenotype.Frontiers in neuroscience · 2023Review
- Phosphoproteomic of the acetylcholine pathway enables discovery of the PKC-β-PIX-Rac1-PAK cascade as a stimulatory signal for aversive learning.Molecular psychiatry · 2022Article
- Differential Transcriptome Profiling Unveils Novel Deregulated Gene Signatures Involved in Pathogenesis of Alzheimer's Disease.Biomedicines · 2022Article
- Artificial intelligence framework identifies candidate targets for drug repurposing in Alzheimer's disease.Alzheimer's research & therapy · 2022Article
- Cdc42/Rac Interactive Binding Containing Effector Proteins in Unicellular Protozoans With Reference to Human Host: Locks of the Rho Signaling.Frontiers in genetics · 2022Review
- Article
- PAK4 suppresses motor neuron degeneration in hSOD1Cell proliferation · 2021Article
- Therapeutic and Mechanistic Effects of Curcumin in Huntington's Disease.Current neuropharmacology · 2021Review
- A Combined Proteomics and Bioinformatics Approach Reveals Novel Signaling Pathways and Molecular Targets After Intracerebral Hemorrhage.Journal of molecular neuroscience : MN · 2020Article
- Direct Visualization of Actin Filaments and Actin-Binding Proteins in Neuronal Cells.Frontiers in cell and developmental biology · 2020Review
- Effect of PAK Inhibition on Cell Mechanics Depends on Rac1.Frontiers in cell and developmental biology · 2020Article
- Spinal cord motor neuron plasticity accompanies second-degree burn injury and chronic pain.Physiological reports · 2019Article
- Altered Levels of Proteins and Phosphoproteins, in the Absence of Early Causative Transcriptional Changes, Shape the Molecular Pathogenesis in the Brain of Young Presymptomatic Ki91 SCA3/MJD Mouse.Molecular neurobiology · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Developmental cognitive deficits including X-linked mental retardation (XLMR) can be caused by mutations in P21-activated kinase 3 (PAK3) that disrupt actin dynamics in dendritic spines. Neurodegenerative diseases such as Alzheimer disease (AD), where both PAK1 and PAK3 are dysregulated, may share final common pathways with XLMR. Independent of familial mutation, cognitive deficits emerging with aging, notably AD, begin after decades of normal function. This prolonged prodromal period involves the buildup of amyloid-β (Aβ) extracellular plaques and intraneuronal neurofibrillary tangles (NFT). Subsequently region dependent deficits in synapses, dendritic spines and cognition coincide with dysregulation in PAK1 and PAK. Specifically proximal to decline, cytoplasmic levels of actin-regulating Rho GTPase and PAK1 kinase are decreased in moderate to severe AD, while aberrant activation and translocation of PAK1 appears around the onset of cognitive deficits. Downstream to PAK1, LIM kinase inactivates cofilin, contributing to cofilin pathology, while the activation of Rho-dependent kinase ROCK increases Aβ production. Aβ activation of fyn disrupts neuronal PAK1 and ROCK-mediated signaling, resulting in synaptic deficits. Reductions in PAK1 by the anti-amyloid compound curcumin suppress synaptotoxicity. Similarly other neurological disorders, including Huntington disease (HD) show dysregulation of PAKs. PAK1 modulates mutant huntingtin toxicity by enhancing huntingtin aggregation, and inhibition of PAK activity protects HD as well as fragile X syndrome (FXS) symptoms. Since PAK plays critical roles in learning and memory and is disrupted in many cognitive disorders, targeting PAK signaling in AD, HD and XLMR may be a novel common therapeutic target for AD, HD and XLMR.
Identifiers
What OpenQuestion holds
Registered trials
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.