Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphodiesterases (PDE) are a diverse family of enzymes (11 isoforms so far identified) responsible for the degradation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) which are involved in several cellular and biochemical functions. Phosphodiesterase 4 (PDE4) is the major isoform within this group and is highly expressed in the mammalian brain. An inverse association between PDE4 and cAMP levels is the key mechanism in various pathophysiological conditions like airway inflammatory diseases-chronic obstruction pulmonary disease (COPD), asthma, psoriasis, rheumatoid arthritis, and neurological disorders etc. In 2011, roflumilast, a PDE4 inhibitor (PDE4I) was approved for the treatment of COPD. Subsequently, other PDE4 inhibitors (PDE4Is) like apremilast and crisaborole were approved by the Food and Drug Administration (FDA) for psoriasis, atopic dermatitis etc. Due to the adverse effects like unbearable nausea and vomiting, dose intolerance and diarrhoea, PDE4 inhibitors have very less clinical compliance. Efforts are being made to develop allosteric modulation with high specificity to PDE4 isoforms having better efficacy and lesser adverse effects. Interestingly, repositioning PDE4Is towards neurological disorders including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS) and sleep disorders, is gaining attention. This review is an attempt to summarize the data on the effects of PDE4 overexpression in neurological disorders and the use of PDE4Is and newer allosteric modulators as therapeutic options. We have also compiled a list of on-going clinical trials on PDE4 inhibitors in neurological disorders.
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PMID:Phosphodiesterase-4 enzyme as a therapeutic target in neurological disorders. 3267 3

Mycobacterium avium subsp. paratuberculosis (MAP) is an understudied pathogen worldwide with continuous implications in human autoimmune diseases (ADs). The awareness of MAP appears to be low in many places and its research is at infant stage in many countries. The lack of worldwide coverage of the MAP research landscape calls for urgent research attention and prioritization. This present study aimed to assess MAP global research productivity with an emphasis on its implications in ADs via bibliometric and growth analytic frameworks from authors, countries, institutions, international, disciplines and collaboration network perspectives. MAP primary articles were retrieved from the Scopus database and the Web of Science from 1911 to 2019 via title-specific algorithm. Analytic results of dataset yielded a total of 3889 articles from 581 journals and 20.65 average citations per documents. The annual growth rate of MAP research for the period was 6.31%. Based on a country's productivity (articles (%), freq. of publication (%)), the USA (887 (22.81%), 26.72%), and Australia (236 (6.07%), 6.07%) ranked the top 2 countries but Egypt and Germany had the highest average growth rate (AGR, 170%) in the last 3 years. MAP studies are generally limited to Europe, Australia, Asia, South America and few nations in Africa. It had positive growth rate (30%-100%) in relation to type 1 diabetes mellitus and rheumatoid arthritis ADs; food science and technology, immunology, agriculture, pathology, and research and experimental medicine, wildlife, environments, virulence, disease resistance, meat and meat products, osteopontin, waste milk and slurry/sludge digestion subjects; but negative growth (-130% to -30%) in ulcerative colitis and Parkinson's disease and no growth in multiple sclerosis, sarcoidosis, thyroid disorders, psoriasis, and lupus. The mapping revealed a gross lack of collaboration networking in terms of authorship, (intra- and inter-) nationally and institutionally with a generalized collaboration index of 1.82. In conclusion, inadequate resources-, knowledge- and scientific-networking hampered growth and awareness of MAP research globally. The study recommends further research to strengthen evidence of MAP's epidemiologic prevalence in ADs and proffer practical solution(s) for drug development and point-of-care diagnostics amongst other extended themes.
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PMID:Systematic Assessment of Mycobacterium avium Subspecies Paratuberculosis Infections from 1911-2019: A Growth Analysis of Association with Human Autoimmune Diseases. 3278 41

Gene expression dictates fundamental cellular processes and its de-regulation leads to pathological conditions. A key contributor to the fine-tuning of gene expression is Dicer, an RNA-binding protein (RBPs) that forms complexes and affects transcription by acting at the post-transcriptional level via the targeting of mRNAs by Dicer-produced small non-coding RNAs. This review aims to present the contribution of Dicer protein in a wide spectrum of human pathological conditions, including cancer, neurological, autoimmune, reproductive and cardiovascular diseases, as well as viral infections. Germline mutations of Dicer have been linked to Dicer1 syndrome, a rare genetic disorder that predisposes to the development of both benign and malignant tumors, but the exact correlation of Dicer protein expression within the different cancer types is unclear, and there are contradictions in the data. Downregulation of Dicer is related to Geographic atrophy (GA), a severe eye-disease that is a leading cause of blindness in industrialized countries, as well as to psychiatric and neurological diseases such as depression and Parkinson's disease, respectively. Both loss and upregulation of Dicer protein expression is implicated in severe autoimmune disorders, including psoriasis, ankylosing spondylitis, rheumatoid arthritis, multiple sclerosis and autoimmune thyroid diseases. Loss of Dicer contributes to cardiovascular diseases and causes defective germ cell differentiation and reproductive system abnormalities in both sexes. Dicer can also act as a strong antiviral with a crucial role in RNA-based antiviral immunity. In conclusion, Dicer is an essential enzyme for the maintenance of physiology due to its pivotal role in several cellular processes, and its loss or aberrant expression contributes to the development of severe human diseases. Further exploitation is required for the development of novel, more effective Dicer-based diagnostic and therapeutic strategies, with the goal of new clinical benefits and better quality of life for patients.
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PMID:Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies. 3300 56

Neurodegenerative diseases are characterized by the loss of neurons and/or myelin sheath, which deteriorate over time and cause dysfunction. Interleukin 17A is the signature cytokine of a subset of CD4+ helper T cells known as Th17 cells, and the IL-17 cytokine family contains six cytokines and five receptors. Recently, several studies have suggested a pivotal role for the interleukin-17A (IL-17A) cytokine family in human inflammatory or autoimmune diseases and neurodegenerative diseases, including psoriasis, rheumatoid arthritis (RA), Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and glaucoma. Studies in recent years have shown that the mechanism of action of IL-17A is more subtle than simply causing inflammation. Although the specific mechanism of IL-17A in neurodegenerative diseases is still controversial, it is generally accepted now that IL-17A causes diseases by activating glial cells. In this review article, we will focus on the function of IL-17A, in particular the proposed roles of IL-17A, in the pathogenesis of neurodegenerative diseases.
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PMID:Interleukin-17A: The Key Cytokine in Neurodegenerative Diseases. 3313 97


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