Ask about this productRelated genes to: PLP1 antibody
- Gene:
- PLP1 NIH gene
- Name:
- proteolipid protein 1
- Previous symbol:
- SPG2, PLP
- Synonyms:
- GPM6C
- Chromosome:
- Xq22.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-22
- Date modifiied:
- 2016-10-05
Related products to: PLP1 antibody
Related articles to: PLP1 antibody
- Chronic pain, a complex multidimensional disorder, remains a major healthcare issue and a therapeutic challenge. Neuropathic pain is a chronic pain condition that results from damage or dysfunction in the nervous system. While mechanisms of neuropathic pain at the peripheral and spinal cord level have been extensively studied, pain mechanisms in the brain remain underexplored. The amygdala, a limbic brain region, has emerged as a critical brain area for the emotional-affective dimension of pain and pain modulation. Amygdala neuroplasticity has been associated with pain states, but the exact molecular and cellular mechanisms underlying these states and the transition from acute to chronic pain are not well understood. Here, we used the spinal nerve ligation (SNL) model of neuropathic pain in male rats to investigate changes in gene expression in the amygdala at the chronic pain stage using RNA sequencing (RNA-Seq). Two amygdala nuclei, the basolateral (BLA) and central (CeA), were investigated in a hemisphere-dependent manner. We used an integrative approach that focuses on functional significance and cell-type specificity of differentially expressed genes (DEGs) to nominate mechanistic targets for central regulation of chronic pain. Our integrative transcriptomic and bioinformatic analyses identified individual genes (e.g., , , , , , , , , and ), molecular pathways (e.g., cytokine-mediated signaling pathway), biological processes (e.g., myelination, synaptic transmission), and specific cell types (e.g., oligodendrocytes, glutamatergic, and GABAergic neurons) affected by chronic pain. Our results also provide some evidence for the emerging concept of hemispheric lateralization of pain processing in the amygdala. Overall, our study proposes oligodendrocyte dysfunction in the amygdala, neuroimmune signaling in the CeA, and glutamatergic neurotransmission in the BLA as key processes and potential therapeutic targets for the management of chronic neuropathic pain. - Source: PubMed
Publication date: 2026/04/25
Presto PeytonCardenas JulianBustamante ChristianKisby Brent RJi GuangchenPonomareva OlgaNeugebauer VolkerPonomarev Igor - The interplay between Schwann cells (SCs) and vascular endothelial cells (ECs) is widely acknowledged as a crucial determinant of successful peripheral nerve regeneration, yet the key molecular mediators that orchestrate this crosstalk remain poorly defined and mechanistically elusive. This study aims to identify novel regulators of Schwann cell-endothelial cell communication and their functional impact on regeneration. Using in vitro co-culture models, live-cell imaging, and transcriptomic sequencing, we characterized cell interactions and identified the top candidate gene, Plp1. We observed dynamic, directed communication primarily via Schwann cell-derived extracellular vesicles (EVs) and confirmed that PLP1 is packaged into EVs and internalized by recipient ECs. Functionally, Plp1 overexpression in ECs inhibited their proliferation, migration, and tube formation. Meanwhile, Plp1 knockdown in SCs enhanced proliferation and migration but impaired their differentiation. In a rat model of sciatic nerve injury, Plp1 knockdown promoted early angiogenesis but disrupted vascular orientation and myelin compaction. Collectively, this study identifies PLP1 as a novel homeostatic regulator in peripheral nerve regeneration that modulates both SC function and EC behavior while also participating in EV-mediated intercellular communication, thereby uncovering its novel biological roles beyond its well-characterized function as a structural myelin component. - Source: PubMed
Publication date: 2026/05/11
Lu PanjianFeng ShuyueHu MingyueCheng XiyangLi MeiyuanQian TianmeiGu XiaosongWang Hongkui - Membrane Attack Complex/Perforin (MACPF) domain proteins are β-pore forming toxins (β-PFTs) involved in the pathogenesis of various organisms. Among them, Perforin-like proteins (PLPs), produced by Plasmodium species, play essential roles in parasite invasion and egress. Due to increasing drug resistance in Plasmodium, PLPs represent promising but underexplored therapeutic targets, largely due to the lack of structural and mechanistic data. This study investigates the binding and pore formation mechanism of the Plasmodium falciparum PLP1 (PfPLP1), which is expressed during the human life cycle of the parasite. We modeled PfPLP1 structure and performed both all-atom and coarse-grained molecular dynamics simulations in soluble and membrane-associated states. PfPLP1 comprises two domains, a canonical MACPF domain and a β-pleated sheet domain- apicomplexan perforin β-domain (APCβ). Initial membrane binding is mediated by cationic residues at the base of the APCβ domain, which interact with the polar headgroups of the lipids from the host cell membrane. We analyzed the membrane-inserted tetrameric form where water molecules were observed to penetrate between the tetramer and the lipid bilayer, initiating pore opening. During this process, lipids reorganize into a toroidal edge to shield their hydrophobic tails, while water mixes with lipid headgroups in a disordered, heterogeneous fashion. Larger oligomeric assemblies show lateral displacement of lipids and a clear tendency to form pore-like structures. This study provides molecular insights into PfPLP1's membrane binding and pore-forming behavior in both monomeric and oligomeric forms. The outcome of this study would be applicable in understanding pore formation mechanism in other PLPs and similar toxins. - Source: PubMed
Publication date: 2026/05/09
Patil Sanket BDasgupta SubrataBhaumik Prasenjit - Chronic psychosocial stress is a major precipitant of Major Depressive Disorder (MDD), yet the glial mechanisms that translate sustained stress into maladaptive myelin and immune changes remain unclear. Using chronic social defeat stress and single-nucleus RNA sequencing of anterior medial PFC (mPFC) oligodendroglia, we identified a mature-oligodendrocyte cluster almost exclusively from stress-susceptible animals, marked by immune genes (MHCII) and upregulated Pde4b. Integration with a human MDD single-nucleus RNA sequencing dataset confirmed a conserved immune-like oligodendrocyte (ImOL) subset coexpressing Plp1 and Cd74 and enriched for Pde4b. Mechanistically, PDE4 inhibition with crisaborole elevated cAMP-PKA-CREB signaling, blocked IFNγ-induced MHCII expression, and engaged the eIF2α-ATF4/CHOP arm of the integrated stress response (ISR). In vivo modulation of the ISR with ISRIB or guanabenz bidirectionally controlled ImOL prevalence and stress-related behaviors. These findings position Pde4b-cAMP-ISR signaling as a regulator of oligodendroglial immune phenotypes and a promising target to modulate myelination and neuroinflammation in stress-related disorders. - Source: PubMed
Publication date: 2026/05/05
Madeira Miguel MHage ZacharyKoliatsis DimitrisKokkosis Alexandros GNnah KimberlyRhee Alexander JRahme Gilbert JKamvisios KatherineKoromilas Antonis ERosati BarbaraMcKinnon DavidTsirka Stella E - Peripheral nerve injury presents a major therapeutic challenge owing to limited endogenous repair and incomplete functional recovery. Schwann cells (SCs), the principal glia of the peripheral nervous system, support axonal integrity and regeneration, but the post-transcriptional mechanisms regulating their development and reparative function remain poorly defined. Here, we investigated the isoform-specific roles of the RNA-binding protein Quaking (QKI), which is alternatively spliced into nuclear (QKI-5) and cytoplasmic (QKI-6 and QKI-7) variants, in governing human Schwann lineage progression. Using a human pluripotent stem cell-derived Schwann cell precursor (SCP) platform, we found that QKI-6 and QKI-7 are selectively upregulated during SCP-to-SC transition, whereas QKI depletion disrupts SCP viability, differentiation, and splicing fidelity. Transcriptomic and rMATS analysis identified more than 800 QKI-dependent splicing events, including disease-relevant isoform shifts in PLP1 and PMP22. Isoform-specific rescue and gain-of-function assays revealed that QKI-6 supports SCP expansion and mitotic progression, whereas QKI-7 promotes SC maturation and neurotrophic output. In a mouse sciatic nerve transection model, transplantation of QKI-7-overexpressing SCPs or SCs significantly enhanced axonal regeneration, remyelination, and motor recovery compared with unmodified or QKI-6-expressing counterparts. Histological analysis confirmed improved donor cell engraftment, myelin protein expression, and neurotrophin levels in QKI-7-modified grafts. These findings establish a sequential, isoform-dependent mechanism of Schwann lineage control and nominate QKI-7 as a candidate for engineering reparative glial cells with enhanced regenerative capacity. Isoform-targeted modulation of RNA-binding proteins may represent a strategy to overcome intrinsic limitations in glial cell therapy for peripheral nerve disorders. - Source: PubMed
Publication date: 2026/05/01
Kim Han-SeopKim Jae YunLee Ji-YoungJeong Ji EunSeol BinnaChoi Ji EunCho Yee Sook