Neurodegenerative, neurodevelopmental, and psychiatric disorders, as well as epilepsy, affect millions of people. Due to their impact on patients’ quality of life, they represent a major health issue. Natural compounds are arising as new treatments for these diseases. Particularly, glucosinolates (GLS) are secondary metabolites found in Cruciferae family plants. Their basic structure consists of a glucose unit linked to a thiohydroximate-O-sulfonate group and an aliphatic, aralkyl, or indolyl side chain, depending on their precursor amino acid. Specifically, aliphatic GLS derive from methionine, aromatic ones from phenylalanine, and indolic ones from tryptophan. Myrosinase (thioglucoside glucohydrolase) is the crucial enzyme for GLS degradation, leading to the production of isothiocyanates (ITCs). ITCs attracted considerable scientific interest for their protective effects against various diseases, thanks to their antioxidant, anti-inflammatory, and neuroprotective properties. Here, we collected the latest evidence regarding ITC effects in neurodegenerative, neurodevelopmental, and psychiatric disorders, including preclinical and clinical studies published in the last decade. These studies evidenced ITCs’ neuroprotective effects, exerted mainly through antioxidant and anti-inflammatory mechanisms. Thus, ITCs’ integration, also through the diet, may represent a safe and efficacious strategy to improve health and limit the risk of neurological and psychiatric disorders. However, new large-scale trials are needed to determine their therapeutic potential, particularly for diseases with no clinical evidence.

About one billion people worldwide are affected by neurologic disorders. Among the various neurologic disorders, one of the most common is Alzheimer’s disease (AD). AD is a neurodegenerative disorder that progressively affects cognitive functions, disrupting the daily lives of millions of individuals. Mild cognitive impairment (MCI) is often considered a prodromal stage of Alzheimer’s disease. In this article, we retrieved data from the online available dataset GSE63060, which includes transcriptomic data of 329 blood samples, of which there are 104 cognitively normal controls, 80 MCI patients, and 145 AD patients. We used transcriptomic data related to all three groups to perform an over-representation analysis of the gene ontologies followed by a network analysis. The aim of our study is to pinpoint alterations, detectable through a non-invasive method, in biological processes affected in MCI that persist during AD. Our goal is to uncover transcriptomic changes that could support earlier diagnosis and the development of more effective therapeutic strategies, starting from the early stages of the disease, to slow down or mitigate its progression. Our work provides a consistent picture of the transcriptomic unbalance of many genes strongly involved in ribosomal formation and biogenesis and splicing processes both in patients with MCI and with AD.

Oxidative stress is a common feature of neurodegenerative diseases. Different natural compounds mediate neuroprotective effects by activating the Nrf2 antioxidant response. Some isothiocyanates are Nrf2 activators, including Moringin (MOR). In this study, the transcriptional profile of differentiated NSC-34 motor neurons was evaluated after treatment for 48 h and 96 h with concentrations of 0.5, 5, and 10 µM of a new MOR formulation obtained with α-cyclodextrin (α-CD). All the concentrations increased gene expression and cytoplasmic protein levels of Nrf2 at 96 h. However, the highest dose also increased nuclear Nrf2 levels at 96 h. Then, Nrf2 interactors were selected using STRING, and common biological process (BP) terms between the groups were evaluated. α-CD/MOR was able to modulate BP related to responses to oxidative stress, proteostasis, and autophagy. Specifically, the treatment with 10 µM of α-CD/MOR for 96 h induced genes involved in glutathione synthesis and proteasome subunits and reduced the expression of genes related to endoplasmic reticulum stress. Moreover, this group showed the lowest levels of the apoptotic markers Bax, cleaved caspase 9, and cleaved caspase 3. These results indicate the beneficial effects of prolonged α-CD/MOR supplementation that are mediated, at least in part, by Nrf2 activation. Then, α-CD/MOR could be a valuable treatment against neurodegenerative diseases, in particular motor neuron degeneration.

α-Cyclodextrin/Moringin (α-CD/MOR) is an isothiocyanate showing neuroprotective and antioxidant properties. In this work, we studied in differentiated NSC-34 motor neurons cell line the molecular pathways activated following a treatment of 96 h with α-CD/MOR at different doses, namely 0.5, 5 and 10 μM. Taking advantage of comparative transcriptomic analysis, we retrieved the differentially expressed genes (DEGs) and we mapped DEGs to synaptic genes using the SynGO database. Then, we focused on the biological pathways in which they are involved. We observed that the prolonged treatment with α-CD/MOR significantly modulated biological processes and cellular components associated with synaptic organization. Interestingly, the KEGG pathway “Regulation of actin cytoskeleton” was overrepresented, alongside pathways related to synapses and axon guidance. Specifically, SPIA analysis indicated that the “Regulation of actin cytoskeleton” pathway was found to be activated with the highest dose of α-CD/MOR. Moreover, α-CD/MOR also modulated transcription factors involved in synaptic plasticity, such as Creb1. These results could indicate that α-CD/MOR can influence synaptic functions and organization, being involved in synaptic plasticity through the modulation of actin dynamics.