Amyotrophic Lateral Sclerosis (ALS) is a severe, progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons, affecting 0.5 to 2.6 per 100,000 people, with a median survival of 2 to 5 years. It is increasingly seen as a multisystem disorder, sharing essential clinicopathological features with Frontotemporal Dementia (FTD). This convergence arises from overlapping molecular processes, including severe oxidative stress, glutamate-mediated excitotoxicity, mitochondrial dysfunction, and widespread aggregated TDP-43 proteinopathy in both sporadic and familial cases. Several key genetic factors have been identified, particularly mutations in C9orf72, SOD1, TARDBP, and FUS, which serve as important targets for novel treatments, such as Tofersen, a recently approved SOD1-specific antisense oligonucleotide (ASO) gene therapy. Additionally, there is increasing evidence of the gut–brain connection. Dysbiosis, involving species such as Akkermansia muciniphila, and lower levels of neuroprotective metabolites, such as nicotinamide, may affect the course of the disease. As a result, treatment strategies are shifting toward a personalized approach. This includes using gene therapy, ranging from ASOs and RNA interference (RNAi) to new CRISPR-based genome editing. It also involves exploring microbiome-modulating treatments, such as specific probiotics and Fecal Microbiota Transplantation (FMT). While microbiome and gene therapies remain largely experimental, their potential is promising, as highlighted by the recent approval of Tofersen. These novel approaches could be further enhanced and guided by more robust diagnostic criteria and by investigating early multimodal treatment strategies to slow the progression of this complex disease.

Background/Objectives: Biotic and abiotic stresses have a negative impact on agriculture worldwide, decreasing crop production. L-type LecRLKs are an important subgroup of the plant receptor-like kinases (RLKs) protein family that aids plants in resisting a variety of biotic and abiotic stressors. However, genome-wide identification and characterization of L-type LecRLK genes and their regulatory elements have not been studied in a model plant, M. truncatula. Methods: This integrated bioinformatic study identified L-type MtLecRLK candidate genes in M. truncatula and characterized them through phylogenetic analysis, domain and gene structure analysis, subcellular localization prediction, gene duplication and chromosomal distribution analysis, Ka/Ks ratio calculation, and identification of cis-regulatory elements, transcription factors, gene ontology terms, and microRNA targets, together with expression data analysis. Results: The analysis revealed 40 L-type MtLecRLK candidate genes in M. truncatula. Phylogenetic analysis classified these genes into six groups (I–VI) and showed the evolutionary relationship between A. thaliana, soybean, and M. truncatula. Domain and gene structure analyses of MtLecRLKs revealed a conserved lectin_legB domain, which has previously been associated with stress tolerance, and showed that 82.5% of MtLecRLKs lack introns. MtLecRLKs have been found to be abundant in the plasma membrane according to subcellular location analyses. Gene duplication and chromosome results of MtLecRLKs revealed that both segmental and tandem duplications may enable family elongation, whereas Ka/Ks ratio analysis indicated that the genes might undergo strong purifying selection. Cis-elements MYB, WRKY, and ABRE; transcription factors CPP and G2-like; gene ontology term stress response; and microRNAs mtr-miR2089, mtr-miR2118, and mtr-miR5558 were identified, and 35% of MtLecRLKs are overexpressed in expression data, which has been found from related analyses and plays a role in various stress responses across studies. Conclusions: These findings propose promising gene candidates correlated with stress adaptation in M. truncatula research and shed insight into the evolution and functional diversity of L-type LecRLKs in plants.