Multiple Sclerosis (MS) is, to date, an incurable disease of the nervous system characterized by demyelination. Several genetic mutations are associated with the disease but they are not able to explain all the diagnosticated cases. Thus, it is suggested that altered gene expression may play a role in human pathologies. In this review, we explored the role of the transcriptomic profile in MS to investigate the main altered biological processes and pathways involved in the disease. Herein, we focused our attention on RNA-seq methods that in recent years are producing a huge amount of data rapidly replacing microarrays, both with bulk and single-cells. The studies evidenced that different MS stages have specific molecular signatures and non-coding RNAs may play a key role in the disease. Sex-dependence was observed before and after treatments used to alleviate symptomatology activating different biological processes in a drug-dependent manner. New pathways, such as neddylation, were found deregulated in MS and inflammation was linked to neuron degeneration areas through spatial transcriptomics. It is evident that the use of RNA-seq in the study of complex pathologies, such as MS, is a valid strategy to shed light on new involved mechanisms.

Alzheimer’s disease (AD) is an incurable neurodegenerative disease diagnosed by clinicians through healthcare records and neuroimaging techniques. These methods lack sensitivity and specificity, so new antemortem non-invasive strategies to diagnose AD are needed. Herein, we designed a machine learning predictor based on transcriptomic data obtained from the blood of AD patients and individuals without dementia (non-AD) through an 8 × 60 K microarray. The dataset was used to train different models with different hyperparameters. The support vector machines method allowed us to reach a Receiver Operating Characteristic score of 93% and an accuracy of 89%. High score levels were also achieved by the neural network and logistic regression methods. Furthermore, the Gene Ontology enrichment analysis of the features selected to train the model along with the genes differentially expressed between the non-AD and AD transcriptomic profiles shows the “mitochondrial translation” biological process to be the most interesting. In addition, inspection of the KEGG pathways suggests that the accumulation of β-amyloid triggers electron transport chain impairment, enhancement of reactive oxygen species and endoplasmic reticulum stress. Taken together, all these elements suggest that the oxidative stress induced by β-amyloid is a key feature trained by the model for the prediction of AD with high accuracy.

Childhood obesity is constantly increasing around the world, and it has become a major public health issue. Considerable evidence indicates that overweight and obesity are important risk factors for the development of comorbidities such as cognitive decline, neuroinflammation and neurodegenerative diseases. It is known that during obesity, adipose tissue undergoes immune, metabolic and functional changes which could induce a neuroinflammatory response of the central nervous system (CNS). In this context, to inspect if obesity can start to trigger the neuroinflammation from a pediatric age, we surgically collected and analyzed adipose tissue from the periumbilical area of three obese children (AT-OB) and two normal-weight children (AT-Ctrl). We considered the transcriptomic profile of our samples to detect alterations in different biological processes that might be also involved in the inflammatory and neuroinflammatory response. Our results show alterations of lipid and fatty acids metabolism in AT-OB compared to the AT-Ctrl. We also observed an onset of inflammatory response in AT-OB. Interestingly, among the genes involved in neuroinflammation, GRN and SMO were upregulated, while IFNGR1 and SNCA were downregulated. Our study highlights that obesity may trigger inflammation and neuroinflammation from a pediatric age.

Neurological disorders such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, and schizophrenia are associated with altered neuronal excitability, resulting from dysfunctions in the molecular architecture and physiological regulation of ion channels and synaptic transmission. Ion channels and synapses are regarded as suitable therapeutic targets in modern pharmacology. Cannabinoids have received great attention as an original therapeutic approach for their effects on human health due to their ability to modulate the neurotransmitter release through interaction with the endocannabinoid system. In our study, we explored the effect of cannabinol (CBN) through next-generation sequencing analysis of NSC-34 cell physiology. Our findings revealed that CBN strongly influences the ontologies related to ion channels and synapse activity at all doses tested. Specifically, the genes coding for calcium and potassium voltage-gated channel subunits, and the glutamatergic and GABAergic receptors (Cacna1b, Cacna1h, Cacng8, Kcnc3, Kcnd1, Kcnd2, Kcnj4, Grik5, Grik1, Slc17a7, Gabra5), were up-regulated. Conversely, the genes involved into serotoninergic and cholinergic pathways (Htr3a, Htr3b, Htr1b, Chrna3, Chrnb2, Chrnb4), were down-regulated. These findings highlight the influence of CBN in the expression of genes involved into ion influx and synaptic transmission.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein aggregates, known as Lewy bodies. It is known that mitochondria dysfunctions, including impaired localization, transport and mitophagy, represent features of PD. Cannabinoids are arising as new therapeutic strategies against neurodegenerative diseases. In this study, we aimed to evaluate the potential protective effects of cannabinol (CBN) pre-treatment in an in vitro PD model, namely retinoic acid-differentiated SH-SY5Y neuroblastoma cells treated with 1-methyl-4-phenylpyridinium (MPP⁺). With this aim, we performed a transcriptomic analysis through next-generation sequencing. We found that CBN counteracted the loss of cell viability caused by MPP⁺ treatment. Then, we focused on biological processes relative to mitochondria functions and found that CBN pre-treatment was able to attenuate the MPP⁺-induced changes in the expression of genes involved in mitochondria transport, localization and protein targeting. Notably, MPP⁺ treatment increased the expression of the genes involved in PINK1/Parkin mitophagy, while CBN pre-treatment reduced their expression. The results suggested that CBN can exert a protection against MPP⁺ induced mitochondria impairment.

Background and objectives: Alzheimer’s disease (AD) is the most common form of dementia characterized by memory loss and executive dysfunction. To date, no markers can effectively predict the onset of AD and an early diagnosis is increasingly necessary. Age represents an important risk factor for the disease but it is not known whether it is the trigger event. Materials and Methods: We downloaded transcriptomic data related to post-mortem brain of thirty samples gathered as young without AD (Young), old without AD (Old), and old suffering from AD (OAD) groups. Results: Our results showed that steroid biosynthesis was enriched and associated with aging, while sphingolipid metabolism was related to both aging and AD. Specifically, sphingolipid metabolism is involved in the deregulation of CERS2, UGT8, and PLPP2. These genes are downregulated in Young and Old groups as compared with upregulated between Old and OAD groups. Moreover, the analysis of the interaction networks revealed that GABAergic synapse and Hippo signaling pathways were altered in AD condition along with mitochondrial metabolism and RNA processing. Conclusions: Observing the particular trend of genes related to sphingolipid metabolism that are downregulated during normal aging and start to be upregulated with the onset of AD, we suppose that sphingolipids could be early markers for the disease.