The technological and scientific progress that we have experienced in recent years has contributed to characterization of the complex processes underlying human biology and evolution ....
The growing and rapid development of high-throughput sequencing technologies have allowed a greater understanding of the mechanisms underlying gene expression regulation. Editing the epigenome and ...epitranscriptome directs the fate of the transcript influencing the functional outcome of each mRNA. In this context, non-coding RNAs play a decisive role in addressing the expression regulation at the gene and chromosomal levels. Long-noncoding RNAs, consisting of more than 200 nucleotides, have been shown to act as epigenetic regulators in several key molecular processes involving neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease. Long-noncoding RNAs are abundantly expressed in the central nervous system, suggesting that their deregulation could trigger neuronal degeneration through RNA modifications. The evaluation of their diagnostic significance and therapeutic potential could lead to new treatments for these diseases for which there is no cure.
Angiotensin-converting enzyme 2 (ACE2) has been recognized as the entry receptor of the novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Structural and sequence variants in
gene ...may affect its expression in different tissues and determine a differential response to SARS-Cov-2 infection and the COVID-19-related phenotype. The present study investigated the genetic variability of
in terms of single nucleotide variants (SNVs), copy number variations (CNVs), and expression quantitative loci (eQTLs) in a cohort of 268 individuals representative of the general Italian population. The analysis identified five SNVs (rs35803318, rs41303171, rs774469453, rs773676270, and rs2285666) in the Italian cohort. Of them, rs35803318 and rs2285666 displayed a significant different frequency distribution in the Italian population with respect to worldwide population. The eQTLs analysis located in and targeting
revealed a high distribution of eQTL variants in different brain tissues, suggesting a possible link between
genetic variability and the neurological complications in patients with COVID-19. Further research is needed to clarify the possible relationship between
expression and the susceptibility to neurological complications in patients with COVID-19. In fact, patients at higher risk of neurological involvement may need different monitoring and treatment strategies in order to prevent severe, permanent brain injury.
One of the main challenges for healthcare systems is the increasing prevalence of neurodegenerative pathologies together with the rapidly aging populations. The enormous progresses made in the field ...of biomedical research and informatics have been crucial for improving the knowledge of how genes, epigenetic modifications, aging, nutrition, drugs and microbiome impact health and disease. In fact, the availability of high technology and computational facilities for large-scale analysis enabled a deeper investigation of neurodegenerative disorders, providing a more comprehensive overview of disease and encouraging the development of a precision medicine approach for these pathologies. On this subject, the creation of collaborative networks among medical centers, research institutes and highly qualified specialists can be decisive for moving the precision medicine from the bench to the bedside. To this purpose, the present review has been thought to discuss the main components which may be part of precise and personalized treatment programs applied to neurodegenerative disorders. Parkinson Disease will be taken as an example to understand how precision medicine approach can be clinically useful and provide substantial benefit to patients. In this perspective, the realization of web-based networks can be decisive for the implementation of precision medicine strategies across different specialized centers as well as for supporting clinical/therapeutical decisions and promoting a more preventive and participative medicine for neurodegenerative disorders. These collaborative networks are essentially addressed to find innovative, sustainable and effective strategies able to provide optimal and safer therapies, discriminate at risk individuals, identify patients at preclinical or early stage of disease, set-up individualized and preventative strategies for improving prognosis and patient's quality of life.
Abstract The actions of nutrients and related compounds on age-related macular degeneration (AMD) are explained in this review. The findings from 80 studies published since 2003 on the association ...between diet and supplements in AMD were reviewed. Antioxidants and other nutrients with an effect on AMD susceptibility include carotenoids (lutein and zeaxanthin, β -carotene), vitamins (vitamin A, E, C, D, B), mineral supplements (zinc, copper, selenium), dietary fatty acids monounsaturated fatty acids, polyunsaturated fatty acids (PUFA both omega-3 PUFA and omega-6 PUFA), saturated fatty acids and cholesterol, and dietary carbohydrates. The literature revealed that many of these antioxidants and nutrients exert a protective role by functioning synergistically. Specifically, the use of dietary supplements with targeted actions can provide minimal benefits on the onset or progression of AMD; however, this does not appear to be particularly beneficial in healthy people. Furthermore, some supplements or nutrients have demonstrated discordant effects on AMD in some studies. Since intake of dietary supplements, as well as exposure to damaging environmental factors, is largely dependent on population habits (including dietary practices) and geographical localization, an overall healthy diet appears to be the best strategy in reducing the risk of developing AMD. As of now, the precise mechanism of action of certain nutrients in AMD prevention remains unclear. Thus, future studies are required to examine the effects that nutrients have on AMD and to determine which factors are most strongly correlated with reducing the risk of AMD or preventing its progression.
Pharmacogenomic studies allowed the reasons behind the different responses to treatments to be understood. Its clinical utility, in fact, is demonstrated by the reduction in adverse drug reaction ...incidence and the improvement of drug efficacy. Pharmacogenomics is an important tool that is able to improve the drug therapy of different disorders. In particular, this review will highlight the current pharmacogenomics knowledge about biologics and small-molecule treatments for psoriasis. To date, studies performed on genes involved in the metabolism of biological drugs (tumor necrosis factor inhibitors and cytokines inhibitors) and small molecules (apremilast, dimethyl fumarate, and tofacitinib) have provided conflicting results, and further investigations are necessary in order to establish a set of biomarkers to be introduced into clinical practice.
Hexanucleotide expansion in
C9orf72
has been related to several phenotypes to date, complicating the clinical recognition of these neurodegenerative disorders. An early diagnosis can improve the ...management of patients, promoting early administration of therapeutic supportive strategies. Here, we report known clinical presentations of
C9orf72
-related neurodegenerative disorders, pointing out suggestive phenotypes that can benefit the genetic characterization of patients. Considering the high variability of
C9orf72
-related disorder, frequent and rare manifestations are described, with detailed clinical, instrumental evaluation, and supportive therapeutical approaches. Furthermore, to improve the understanding of molecular pathways of the disease and potential therapeutical targets, a detailed description of the cellular mechanisms related to the pathological effect of
C9orf72
is reported. New promising therapeutical strategies and ongoing studies are reported highlighting their molecular role in cellular pathological pathways of
C9orf72
. These therapeutic approaches are particularly promising because they seem to stop the disease before neuronal damage. The knowledge of clinical and molecular features of
C9orf72
-related neurodegenerative disorders improves the therapeutical application of known strategies and will lay the basis for the development of new potential therapies.
In the present study, we investigated the distribution of genetic variations in
and
genes, which may be employed as prognostic and pharmacogenetic biomarkers for COVID-19 and neurodegenerative ...diseases. The study was performed on 271 samples representative of the Italian general population and identified seven variants (rs140764737, rs142164099, rs2069849, rs142759801, rs190436077, rs148171375, rs13306435) in
and five variants (rs2228144, rs2229237, rs2228145, rs28730735, rs143810642) within
, respectively. These variants have been predicted to affect the expression and binding ability of IL6 and IL6R. Ingenuity Pathway Analysis (IPA) showed that IL6 and IL6R appeared to be implicated in several pathogenetic mechanisms associated with COVID-19 severity and mortality as well as with neurodegenerative diseases mediated by neuroinflammation. Thus, the availability of
-
-related biomarkers for COVID-19 may be helpful to counteract harmful complications and prevent multiorgan failure. At the same time,
-
-related biomarkers could also be useful for assessing the susceptibility and progression of neuroinflammatory disorders and undertake the most suitable treatment strategies to improve patients' prognosis and quality of life. In conclusion, this study showed how IL6 pleiotropic activity could be exploited to meet different clinical needs and realize personalized medicine protocols for chronic, age-related and modern public health emergencies.
Parallel and massive sequencing of total RNA samples derived from different samples are possible thanks to the use of NGS (Next Generation Sequencing) technologies. This allowed characterizing the ...transcriptomic profile of both cell and tissue populations, increasing the knowledge of the molecular pathological processes of complex diseases, such as neurodegenerative diseases (NDs). Among the NDs, Amyotrophic Lateral Sclerosis (ALS) is caused by the progressive loss of motor neurons (MNs), and, to date, the diagnosis is often made by exclusion because there is no specific symptomatologic picture. For this reason, it is important to search for biomarkers that are clinically useful for carrying out a fast and accurate diagnosis of ALS. Thanks to various studies, it has been possible to propose several molecular mechanisms associated with the disease, some of which include the action of non-coding RNA, including circRNAs, miRNAs, and lncRNAs which will be discussed in the present review. The evidence analyzed in this review highlights the importance of conducting studies to better characterize the different ncRNAs in the disease to use them as possible diagnostic, prognostic, and/or predictive biomarkers of ALS and other NDs.
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