LM11A-31 decreased mHtt aggregates in SH-SY5Y cells expressing mHtt (exon 1 with 74 CAG repeats) and increased autophagic/lysosomal activity, as indicated by altered levels of relevant markers (e.g., p62/SQSTM1 and mature cathepsin D) and increased autophagy flux.
Neurotherapeutics. 2025 Mar;22(2):e00495
Human retinal endothelial (HRE) cells
200 nmol/L
To investigate the effect of LM11A-31 on proNGF-mediated cell permeability. Results showed that LM11A-31 significantly attenuated proNGF-mediated increase in HRE cell permeability.
Diabetologia. 2019 Aug;62(8):1488-1500
microglia
10 nM
7 days
To evaluate the effects of LM11A-31 on FIV-infected feline microglia. LM11A-31 reduced FIV-induced microglial accumulation but no direct effects were observed in purified microglial cultures.
J Neuroimmune Pharmacol. 2012 Jun;7(2):388-400
astrocytes
10 nM
7 days
To evaluate the effects of LM11A-31 on FIV-infected feline astrocytes. LM11A-31 reduced FIV-induced morphological changes in astrocytes and suppressed calcium destabilization.
J Neuroimmune Pharmacol. 2012 Jun;7(2):388-400
feline neurons
10 nM
7 days
To evaluate the neuroprotective effects of LM11A-31 on FIV-infected feline neurons. LM11A-31 significantly reduced FIV-induced neuronal damage, including dendritic beading and neuronal shrinkage, and restored MAP-2 staining intensity.
J Neuroimmune Pharmacol. 2012 Jun;7(2):388-400
microglia
10 nM
1 hour
Suppressed HIV gp120-induced neurotoxic factor release, with a secretory profile similar to macrophages
J Neuroimmune Pharmacol. 2022 Jun;17(1-2):242-260
monocyte-derived macrophages (MDM)
10 nM
overnight
Suppressed HIV gp120-induced release of neurotoxic factors and induced a shift to a ruffled macrophage phenotype
J Neuroimmune Pharmacol. 2022 Jun;17(1-2):242-260
human retinal endothelial cells (HREs)
200 nM
12 hours
LM11A-31 treatment enhanced the secretome of MSCs, significantly increasing the release of SDF-1α, VEGF, and NGF, and improved the angiogenic response of HREs
Int J Mol Sci. 2021 Jan 15;22(2):829
mononuclear cells from synovial fluid (SFMC) of patients with JIA
10 nM
1 hour
inhibition of proNGF-induced IL-6 production
RMD Open. 2017 Sep 12;3(2):e000441
Detroit-562 cells
4 μM
Cells. 2019 Sep 28;8(10):1167
Cal-27 cells
4 μM
Cells. 2019 Sep 28;8(10):1167
PE/CA-PJ15 cells
4 μM
7 hours
inhibition of cell motility
Cells. 2019 Sep 28;8(10):1167
LM11A-31 2HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
R6/2 and zQ175dn Huntington's disease model mice
Oral gavage
25, 50, and 100 mg/kg (R6/2 mice); 10, 25, and 50 mg/kg (zQ175dn mice)
R6/2 mice: once daily for 7 weeks; zQ175dn mice: once or twice daily for 4 months
LM11A-31 reduced mHtt aggregates in the striatum of R6/2 and zQ175dn mice, increased AMPK activation, normalized p62/SQSTM1 and LC3II levels, enhanced LAMP1, and decreased LC3B association with mHtt.
Neurotherapeutics. 2025 Mar;22(2):e00495
Sprague-Dawley rats
Streptococcus pneumoniae meningitis model
Intranasal administration
15 μg/60 μL/day
Once daily for three consecutive days pretreatment
LM11A-31 pretreatment significantly alleviated S. pneumoniae-induced clinical severity, histopathological injury and the activation of astrocytes and microglia. LM11A-31 pretreatment also significantly ameliorated neuronal apoptosis and necrosis. Moreover, blocking p75NTR with LM11A-31 decreased the expression of inflammation-related transcription factors (NF-κBp65, C/EBPβ) and proinflammatory cytokines/mediators (IL-1β, TNF-α, IL-6 and iNOS).
J Neuroinflammation. 2021 Nov 2;18(1):253
C57BL/6J mice
Streptozotocin-induced diabetic model
Oral gavage
50 mg/kg
Every 48 hours for 4 weeks
To evaluate the effect of LM11A-31 on diabetes-induced retinal vascular permeability and inflammation. Results showed that LM11A-31 significantly mitigated diabetes-induced increase in retinal vascular permeability and reduced expression of inflammatory mediators TNF-α and IL-1β.
Diabetologia. 2019 Aug;62(8):1488-1500
Mouse
Alzheimer's disease model mice
Oral gavage
50 mg/kg/day
Once daily for 3 months
To evaluate the modulation of neuroinflammation by LM11A-31 in Alzheimer's disease model mice. Results showed that LM11A-31 treatment significantly reduced TSPO-PET signal in the cortex and hippocampus of mice, corresponding with decreased levels of TSPO immunostaining and microglial Iba1 immunostaining.
Theranostics. 2017 Mar 24;7(6):1422-1436
Mice
P301S tauopathy mouse model
Oral gavage
50 mg/kg
Five days per week for 3 months
LM11A-31 reduced excess activation of hippocampal cdk5 and JNK kinases, calpain activity, cofilin phosphorylation, tau phosphorylation, acetylation and cleavage, accumulation of multiple forms of insoluble tau aggregates and filaments, and microglial activation, while improving hippocampal behavioral performance
Acta Neuropathol Commun. 2020 Sep 5;8(1):156
Mice
Unilateral sciatic denervation model
Oral
75mg/kg/day
Once daily for one week
Inhibition of p75NTR significantly reduced JNK activation and inflammatory cytokines in the denervated muscle.
Life Sci. 2021 Dec 1;286:120067
Mice
Retinal ischemia/reperfusion (I/R) injury model
Oral
50 mg/kg/day
Every other day for 15 days
LM11A-31 significantly mitigated the decline in visual acuity post retinal I/R injury
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