A significant portion of patients who are afflicted with lysosomal storage diseases (LSDs) encounter neurological manifestations, including cognitive issues and developmental delay, seizures, psychiatric issues, and an overall neurodegenerative decline. In order to enhance the development of effective therapies for these symptoms, it is imperative that we allude to the neuropathophysiology that underlies these manifestations. These distinct neurological and developmental features are particularly evident in patients with Alpha-Mannosidosis (AM), a type of LSD. However, there is limited published information regarding the mechanisms and pathophysiology of these presentations in patients with this condition. Although the precise impact of lysosomal storage on the biogenesis and functioning of neuronal cells has not been clearly defined, recent studies have placed emphasis on the significance of synaptic defects influencing this dysfunction. These defects encompass changes in synaptic spines, proteins, and vesicles, as well as postsynaptic densities that potentially precipitate functional disruptions in synaptic transmission and neurodegeneration. Ultimately, this cascade is thought to result in extensive neuronal loss and, consequently, the onset of cognitive manifestations. Uncovering the effects on synaptic components in LSDs with neurological symptoms like AM will enable a better understanding of disease progression. It will also allow us to identify critical targets for therapeutic intervention and the determination of optimal time frames for targeted treatments, as well as the effects of these treatments on mitochondrial function. The available therapeutic modalities in AM are not a definitive cure for affected patients, but rather an attempt to reduce the symptomatic severity in their presentation, while aiming to regress/slow down disease progression. This review will aim to discuss and rationalize the current treatment approaches in place for AM patients in relation to their effects on the improvement of neurocognitive symptoms in affected AM individuals.

Twin studies are cutting-edge design methodologies proper to behavioral genetics that aim to investigate how the interplay between genetic and environmental factors can concur to explain individual differences in psychopathology, temperamental traits, and behavior. This particular research design has been widely applied to the study of comorbidity between internalizing (INT) and externalizing (EXT) symptoms, especially in childhood and adolescence. Notably, the high co-occurrence of symptoms of both these diagnostic domains has led to the hypothesis that at their basis, there might be one single latent common susceptibility factor, namely p factor. Twin studies have contributed to marking a relevant turning point in this regard by highlighting the consistent genetic nature of this factor. In light of these premises, the present narrative review aims to outline the path for future twin studies in investigating the comorbidity between Cognitive Disengagement Syndrome (CDS) and INT-EXT disorders, examining the evidence supporting this need and its clinical implications. Since CDS has not been recognized as a stand-alone syndrome until very recently, research on this condition is still in its infancy and the etiological factors at the basis of its comorbidity with INT-EXT are still unclear. Being aware of the causal factors underneath the comorbidity between INT-EXT might pave the way for improving assessment diagnostic procedures as well as setting up preventive interventions for CDS.

Prostate cancer stands as the most prevalent cancer globally, constituting 21% of all cancer diagnoses in male patients. Urgent optimization of prostate cancer care is essential, given that this disease claims 345,000 lives every year. These innovative approaches hold substantial promise for both researchers and patients, representing a beacon of hope in the inhibitory act against prostate cancer. Prostate cancer's gradual advancement deems it suitable for immune therapy, but trials in metastatic cases show limited effectiveness, likely due to compromised immunity. Hindered by defective cellular responses, an immune-suppressive microenvironment, emerging evidence and breakthroughs, such as CAR-T therapy, inspire cautious optimism for advanced prostate cancer immunotherapy. Tumors utilize tactics to escape immune recognition, promoting the proliferation of MDSCs, Treg cells, and TAMs. Immunotherapy targets prostate cancer by mostly expressed target proteins and overexpressed target proteins. Immune cells play a role in tumor development and metastasis in advanced prostate cancer. Modulating the tumor microenvironment presents therapeutic possibilities. Certain prostate cancer types exhibit potential responses to immune checkpoint inhibitors, yet obstacles remain, necessitating additional research for enhanced efficacy. Immunotherapy faces hurdles in prostate cancer - limited inflammation, scarce antigens, and a resistant microenvironment. Grasping resistance intricacies is pivotal. The identification of DNA's helical structure propelled global progress in disease treatment through gene therapy. Choosing gene therapy vectors is critical; viruses are potent but toxic, while nonviral options, though less toxic, encounter barriers affecting transfection. In the realm of prostate cancer treatment, immunotherapy and gene therapy are emerging as increasingly viable options.

Long non-coding RNAs (lncRNAs) are a class of RNA transcripts that are long (i.e., more than 200 nucleotides) and not translated into proteins. They have recently emerged as potential treatment targets for numerous disorders due to their involvement in multiple cellular functions such as gene regulation, epigenetic modulation, and chromatin organization. This review highlights the current state of lncRNA-based therapeutics, the potential of lncRNAs as drug targets for treating human diseases, the various strategies and types of RNA-based therapeutics, and the complications of developing lncRNA-based drugs. We conclude that lncRNA-based therapeutics represent a promising class of drugs that can potentially treat various human diseases and that further research is needed to fully realize their therapeutic potential.

Cardiovascular diseases (CVDs) remain one of the leading causes of morbidity and mortality worldwide, with genetics being a major risk factor. Genetic cardiovascular disease can occur either because of single variant (Mendelian) or polygenic influences and has been linked to inherited cardiovascular conditions (ICC) such as arrhythmias, cardiomyopathies, dyslipidemias, and aortopathies which are significant factors leading to sudden cardiac death in young adults. Timely screening, diagnosis, and management of ICC can not only provide life-saving treatment to a patient, but also identify at-risk family members. The field of pharmacogenomics (PGx) helped to understand the variable action of medications such as clopidogrel, aspirin, warfarin, and statin according to genotype. Newer technologies such as multi-omics can combine data from multiple sources such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiome. These advancements can contribute to the development of polygenic prediction scores and precision medicine tailored to individual genotypes. Substantial strides have been made in genetic-based therapeutics, gene editing technologies, and drug delivery systems, which have significantly expanded treatment options for patients with acquired or inherited CVDs. Although variable, the country- and society-specific guidelines on genetic testing for ICC and PGx and treatment are being continuously updated to keep up with ongoing research in the field. Along with appropriate knowledge, other factors including cost and availability of genetic testing play a vital role in the usage by both physicians and patients. With the advent of newer genetic testing for CVDs, a key factor is the availability of genetic counselors (GCs) who are specifically trained in cardiovascular genomics. The current review provides a concise summary of the major influences of genetics in the diagnosis and treatment of CVDs.