COG 133 / Cognosci - LARVOL DELTA

COG133 ameliorates depression-like behaviors in mice by inhibiting p38 MAPK-mediated neuroinflammation. (PubMed, Brain Behav Immun) - "Pharmacological modulation of p38 MAPK further confirmed that this pathway is essential for COG133-mediated behavioral and cellular recovery. Together, these findings identify COG133 as a promising peptide candidate for the treatment of depression through modulation of the p38 MAPK-mediated neuroinflammation axis."

Journal • Preclinical • CNS Disorders • Depression • Inflammation • Mood Disorders • Psychiatry • APOE • ATF2 • MAP2K3

TREM2 activation suppresses central sensitisation by promoting autophagy in a chronic migraine model with recurrent nitroglycerin stimulation in mice. (PubMed, Br J Pharmacol) - "These data show that TREM2 plays a protective role in CM by modulating microglial activation and autophagy in the TNC via the mTOR/p70s6k pathway."

Journal • Preclinical • CNS Disorders • Immunology • Inflammation • Migraine • Pain • FOS • TREM2

TREM2 Facilitates Myelin Debris Clearance but Exacerbates Chronic Inflammation and Fibrosis After Spinal Cord Injury. (PubMed, CNS Neurosci Ther) - "Our study suggests that TREM2 promotes myelin debris clearance but exacerbates chronic inflammation and fibrosis after SCI. These findings underscore the promise of TREM2 as a target for developing effective treatment strategies for SCI."

Journal • CNS Disorders • Fibrosis • Immunology • Inflammation • Orthopedics • TREM2

Therapeutic Potential of the ApoE-Mimicked Peptide COG133: Regulation of miRNA146‑a in Diabetic Fibroblasts and Antibacterial Activity. (PubMed, ACS Omega) - "Antibacterial assays revealed inhibitory effects, with the lowest MIC against Chromobacterium violaceum, and a 55% reduction in Pseudomonas aeruginosa PAO1 biofilm formation. These results suggest that COG133 modulates inflammatory signaling and exhibits antibacterial properties, highlighting its therapeutic potential in supporting wound healing in diabetes."

Journal • Diabetes • Infectious Disease • Inflammation • Metabolic Disorders • APOE • IL6 • MIR146A

Targeting neuroinflammation and PVNCRH neurons: dexmedetomidine liposomes for perioperative neurocognitive disorder with comorbid anxiety. (PubMed, Mater Today Bio) - "Here, a brain-targeted liposomal formulation (D@ACLipo) was developed for the co-delivery of the perioperative sedative dexmedetomidine (DEX) and the microglia-modulating peptide COG1410, incorporating Angiopep-2 to enhance brain penetration. Additionally, in vivo fiber photometry revealed that DEX significantly suppressed corticotropin-releasing hormone (CRH) neuron activity in the paraventricular nucleus (PVN), contributing to its anxiolytic effect. These findings highlight a promising translational nanotherapeutic strategy for the dual prevention of PND and anxiety by targeting molecular signaling pathways and neural circuits."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Inflammation • Psychiatry • TLR4

ApoE COG 133 mimetic peptide improves survival, infection burden, and Clostridioides difficile toxin-A-induced intestinal damage in mice. (PubMed, Exp Biol Med (Maywood)) - "This suggests a potential anti-inflammatory role of COG133 in CDI. More studies are neede to these intial findings in depth."

Journal • Preclinical • Gastrointestinal Disorder • Infectious Disease • Inflammation • Inflammatory Bowel Disease • APOE

DRUG SCREENING IDENTIFIES BMS-202, COG1410, AND FINGOLIMOD AS BBBPENETRANT COMPOUNDS WITH ANTITUMOR ACTIVITY IN GLIOBLASTOMA CELL LINES (SIOP 2025) - "These findings highlight the therapeutic potential of these drugs for glioblastoma treatment, overcoming traditional barriers and resistance mechanisms. Funding: FAPESP (Grant: 2022/09037-3), INCT BioOncoPed-CNPq (Grant: 406484/2022-8)."

IO biomarker • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • ABCC1 • APOE • NOS1

Modulating Amyloid Pathology-Neural Hyperexcitability Crosstalk for Alzheimer's Disease Therapy. (PubMed, ACS Nano) - "Here, we designed R@AClipo, a nanotherapeutic platform that codelivers the TREM2 agonist peptide COG1410 and the glutamate modulator riluzole via Angiopep-2-modified liposomes capable of crossing the blood-brain barrier. This combinatorial strategy improved cognitive performance and restored neural activity patterns without observable toxicity. Together, these findings support a physiologically compatible strategy that targets the pathological crosstalk between Aβ accumulation and neural hyperexcitability, offering a promising avenue for AD intervention."

Journal • Alzheimer's Disease • CNS Disorders • TREM2

TREM2-mediated neuroinflammatory response is involved in AgNPs-induced ferroptosis in HMC3 cells. (PubMed, Neurotoxicology) - "Treatment with the TREM2 agonist COG 1410 (5μg/mL) significantly upregulated TREM2 expression, attenuated pro-inflammatory factors, and enhanced anti-inflammatory factors. Moreover, TREM2 activation significantly inhibited AgNPs-induced ferroptosis in HMC3 cells, indicating that TREM2-mediated inflammation may play a key role in regulating this process. These findings offer new understanding of AgNPs neurotoxicity and potential therapeutic targets for reducing CNS damage from AgNPs exposure."

Journal • Inflammation • TREM2

COG1410 Alleviated Chronic Sleep Deprivation-Induced Memory Loss by Regulating Microglial Phagocytosis and Inhibiting Hippocampal Inflammation. (PubMed, ACS Chem Neurosci) - "Finally, we downregulated the expression of TREM2 in the hippocampus using small interfering RNA (siRNA), which reduced the protective effect of COG1410 in SD mice. In summary, COG1410 has the potential to prevent SD-induced memory consolidation impairment by maintaining microglial phagocytosis and anti-inflammation in the mouse hippocampus."

Journal • Inflammation • APOE • TREM2

Retraction: Apolipoprotein E-mimetic peptide COG1410 promotes autophagy by phosphorylating GSK-3β in early brain injury following experimental subarachnoid hemorrhage. (PubMed, Front Neurosci) - "[This retracts the article DOI: 10.3389/fnins.2018.00127.]."

Journal • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage • Vascular Neurology • APOE • GSK3B

Protective Effects of COG133 on Carbon Tetrachloride-Induced Acute Liver Injury: Modulation of Inflammation, Apoptosis and Sphingolipid Metabolism. (PubMed, J Cell Mol Med) - "COG133 protects against CCl4-induced liver injury by reducing inflammation, apoptosis and morphological damage, with partial restoration of sphingolipid metabolism. These findings support its potential as a novel therapeutic agent for acute liver injury."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Metabolic Disorders • Oncology • APOE • IL1B • NFKB1 • NOS2 • TGFB1 • TNFA

COG133 peptide-conjugated lipid nanoparticles sensitize medulloblastoma to radiation therapy in mice. (PubMed, J Control Release) - "In this study, we aimed to decrease the dose of irradiation and the proliferation of MB by using Volasertib (VSB), a Polo-like kinase 1 (PLK1) specific inhibitor. Furthermore, COG133-LNPs along with irradiation decreased tumor burden significantly as compared to VSB or radiation alone. To our observation, COG133-LNPs display high potency in killing MB cells and sensitizing them toward radiation therapy."

Journal • Preclinical • Brain Cancer • Cognitive Disorders • Developmental Disorders • Medulloblastoma • Oncology • Solid Tumor • PLK1

Intranasal Administration of a Novel ApoE-Mimetic Peptide-Coated Gold Nanoparticles as Therapy for Ischemic Stroke. (PubMed, CNS Neurosci Ther) - "CS15-GNPs exhibited favorable neuroprotection and biosafety. This study develops an innovative ApoE-mimetic peptide-capped GNPs, which provides a potential strategy for the treatment of ischemic stroke."

Journal • Cardiovascular • Inflammation • Ischemic stroke • APOE

TREM2 Modulates Postoperative Cognitive Function in Aged Mice by Inhibiting the NLRP3/caspase-1 Pathway and Apoptosis via PLCγ2 Activation. (PubMed, Mol Neurobiol) - "Mice subjected to surgery were pre-treated with the TREM2-activating peptide COG1410, and subsequently evaluated for neuroinflammation, neuronal apoptosis, and cognitive function. TREM2 modulates PLCγ2 activity through SYK phosphorylation, thereby alleviating microglial-driven neuroinflammation and neuronal apoptosis, and improving cognitive impairment following surgery. Targeting the TREM2-PLCγ2 pathway presents a promising strategy for the prevention and treatment of POCD."

Journal • Preclinical • Alzheimer's Disease • Cognitive Disorders • Inflammation • IL18 • IL1B • NLRP3 • PLCG2 • SYK

EXPLORING BLOOD-BRAIN BARRIER-PENETRATING DRUGS FOR THE IDENTIFICATION OF NOVEL THERAPIES IN GLIOBLASTOMA (SIOP 2024) - " Seven drugs: Obatoclax (Mesylate), COG1410, Fingolimod, Ozanimod, Lonafarnib, BMS-202 and Bazedoxifene (acetate) were screened out as potential candidates, with consistent efficacy against glioblastoma cells, providing promising avenues for standalone therapies in GBM or as enhancers of existing conventional chemotherapy regimens. This multi-faceted approach aims to develop personalized and effective treatment strategies for the challenging landscape of glioblastoma tumors. This work was supported by FAPESP grant numbers 2022/09037-3, National Council for Scientific and Technological Development (CNPq, MCTI, Brazil) grant number 406484/2022-8 (INCT BioOncoPed)"

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

TREM2 alleviates long-term cognitive dysfunction after subarachnoid hemorrhage in mice by attenuating hippocampal neuroinflammation via PI3K/Akt signaling pathway. (PubMed, Brain Res) - "To explore the protective effects of TREM2, we utilized the TREM2 agonist COG1410 to upregulate TREM2 expression and employed TREM2 knockout (KO) mice to verify the necessity of TREM2 for this protective role. In conclusion, TREM2 upregulation mitigates long-term cognitive dysfunction following SAH by attenuating hippocampal neuroinflammation via the PI3K/Akt signaling pathway. These findings suggest that TREM2 could be a potential therapeutic target for improving cognitive outcomes after SAH."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Hematological Disorders • Inflammation • Subarachnoid Hemorrhage • TREM2

TREM2, a critical activator of pyroptosis, mediates the anti‑tumor effects of piceatannol in uveal melanoma cells via caspase 3/GSDME pathwayTREM2, a critical activator of pyroptosis, mediates the anti‑tumor effects of piceatannol in uveal melanoma cells via caspase 3/GSDME pathway. (PubMed, Int J Mol Med) - "As an agonist of TREM2, COG1410‑mediated TREM2 upregulation inhibited proliferation of C918 cells, displaying similar effects to PIC. Furthermore, PIC inhibited tumor growth via regulating the TREM2/caspase 3/GSDME pathway in a mouse model. Collectively, the present study revealed a novel mechanism underlying the inhibitory effects of PIC on UM, providing a potential treatment approach for UM in clinic."

Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CASP3 • CASP9 • CAT • GSDMD • GSDME • IL1B • TREM2

Engineered endolysin of Klebsiella pneumoniae phage is a potent and broad-spectrum bactericidal agent against "ESKAPEE" pathogens. (PubMed, Front Microbiol) - "Our study focuses on engineering endolysins from a Klebsiella pneumoniae phage, fusing them with ApoE23 and COG133 peptides. Our findings advance the field of endolysin engineering, facilitating the customization of these proteins to target specific bacterial pathogens. This approach holds promise for the development of personalized therapies tailored to combat ESKAPEE infections effectively."

Journal • Infectious Disease • Pneumonia

Precise Modulation of Pericyte Dysfunction by a Multifunctional Nanoprodrug to Ameliorate Alzheimer's Disease. (PubMed, ACS Nano) - "Inspired by the elevation of vascular cell adhesion molecule-1 (VCAM-1) and reactive oxygen species (ROS) levels in pericyte lesions, we fabricated a multifunctional nanoprodrug by conjugating the hybrid peptide VLC, a fusion of the VCAM-1 high-affinity peptide VHS and the neuroprotective apolipoprotein mimetic peptide COG1410, to curcumin (Cur) through phenylboronic ester bond (VLC@Cur-NPs) to alleviate complex pericyte-related pathological changes. Consequently, VLC@Cur-NPs markedly increased pericyte regeneration to form a positive feedback loop and thus improved neurovascular function and ultimately alleviated memory defects in APP/PS1 transgenic mice. We present a promising therapeutic strategy for AD that can precisely modulate pericytes and has the potential to treat other cerebrovascular diseases."

Journal • Alzheimer's Disease • CNS Disorders • Vascular Neurology • VCAM1

TREM2 alleviates white matter injury after traumatic brain injury in mice might be mediated by regulation of DHCR24/LXR pathway in microglia. (PubMed, Clin Transl Med) - "We demonstrate that TREM2 has the potential to alleviate WMI following TBI, possibly through the DHCR24/LXR pathway in microglia."

Journal • Preclinical • CNS Disorders • Solid Tumor • Vascular Neurology • TREM2

ApoE Mimetic Peptide COG1410 Kills Mycobacterium smegmatis via Directly Interfering ClpC's ATPase Activity. (PubMed, Antibiotics (Basel)) - "This study sheds light on a unique resistance mechanism against AMPs in mycobacteria, highlighting the pivotal role of ClpC in this process. Unraveling the interplay between COG1410 and ClpC enriches our understanding of AMP-bacterial interactions, offering potential insights for developing innovative strategies to combat antibiotic resistance."

Journal • Infectious Disease • APOE

The role of ApoE in fatty acid transport from neurons to astrocytes under ischemia/hypoxia conditions. (PubMed, Mol Biol Rep) - "In conclusion, ApoE plays an important role in mediating the transport of fatty acids from neurons to astrocytes under ischemia/hypoxia conditions, and this transport mechanism is ApoE isoform dependent. ApoE4 has a low transfer efficiency and may be a potential target for the clinical treatment of neonatal hypoxic-ischemic encephalopathy."

Journal • Cardiovascular • CNS Disorders • Vascular Neurology • APOE • FABP5 • SOD1

Preclinical Evaluation of Tc-MAG-5-Fab Targeting TREM2 in Lung Cancer Mouse Models: A Comparison with Tc-MAG-5-F(ab'). (PubMed, Mol Pharm) - "Previously, we performed TREM2 targeting imaging by using Ga-NOTA-COG1410 or a I-labeled monoclonal antibody (mAb) and F(ab') in mouse models of colon and gastric tumors. The biodistribution results were consistent with the micro-SPECT/CT imaging results. Tc-MAG-5-Fab could clearly display hTREM2 A549 tumors in a short time (1 h) with low uptake in nontumor organs and tissues and thus has clinical application prospects."

Journal • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Solid Tumor • TREM2

COG1410 regulates microglial states and protects retinal ganglion cells in retinal ischemia-reperfusion injury. (PubMed, Exp Eye Res) - "The expression of TREM2 showed an increasing trend after COG1410 administration, but it was not statistically significant. In conclusion, COG1410 regulates microglial states and protects RGCs in retinal IR injury, showing promising potential for the treatment of eye diseases."

Journal • Cardiovascular • Glaucoma • Inflammation • Ophthalmology • Reperfusion Injury • APOE • IL1B • MRC1 • NR4A1 • TNFA • TREM2