👤 Mahdi Rohani

Neuroinflammation is a central contributor to Huntington's disease (HD) pathogenesis and represents a promising therapeutic target. Laquinimod, an oral immunomodulator with demonstrated neuroprotective effects in preclinical models, has been investigated as a potential treatment for HD. This review critically appraises its preclinical and clinical evidence. A systematic search (January 2025) was conducted in PubMed, Scopus, Embase, Cochrane Library, and Web of Science using terms including "Huntington's disease," "laquinimod," and "quinoline-3-carboxylic acid." Preclinical and clinical studies evaluating laquinimod in HD were included. Due to heterogeneity, findings were synthesized qualitatively. Of 2638 records identified, 10 studies met the inclusion criteria. Preclinical data showed laquinimod improved motor function, reduced neuroinflammation, and promoted myelination, likely via microglial modulation, NF-κB suppression, and increased BDNF expression. Effects on myelin integrity and inflammatory markers were inconsistent. In vitro studies showed limited, variable cytokine modulation in HD patient-derived cells. Clinical trials did not demonstrate significant improvements in motor or functional outcomes, though one study reported minor cognitive and behavioral benefits. Preclinical evidence suggests laquinimod may modulate motor, inflammatory, and myelination pathways in HD; however, clinical evidence shows no meaningful benefit. Data on long-term safety remain limited. Larger, well-designed trials using standardized biomarkers are needed to clarify its therapeutic potential. Show less

Probiotics are beneficial microorganisms that modulate various signaling pathways to improve human health status. In this study we aimed to evaluate the precise molecular effects of Lactobacillus spp., Bifidobacterium spp., and a mixture of our native potential probiotics on the autophagy signaling pathway during the presence of inflammation. The evaluation of autophagy gene expression was performed after exposing the HT -29 cell line with the sonicated pathogens and probiotics, before and simultaneously with inflammation induction by quantitative real-time polymerase chain reaction (qPCR) and cytokine assays. The results of the current study showed that our native potential probiotic cocktails could upregulate the expression level of the autophagy genes including pik3c3, atg14, beclin, pik3r4, atg5, atg16, atg7, and atg3 compared with sonicated pathogen treatments, and also these native potential probiotic strains could exert anti-inflammatory effects, especially before inflammation induction. In conclusion, our native potential probiotic cocktail indicated the preventive and therapeutic effect on inflammation, but our selected probiotics could affect autophagy genes stronger before inflammation compared to expose simultaneously with inflammation. Therefore, the administration of probiotics as a prophylactic agent with the least side effects could be considered a suitable treatment for patients with inflammatory-related disease, even before or at the beginning of inflammation. Show less