Diabetes mellitus and Parkinson's disease: dangerous liaisons between insulin and dopamine.
Ontology highlight
ABSTRACT:
SUBMITTER: De Iuliis A
PROVIDER: S-EPMC8504381 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The molecular processes underlying neurodegenerative diseases (such as Alzheimer's Disease - AD) remain poorly understood. There is also an imperative need for disease-modifying therapies in AD since the present treatments, acetylcholinesterase inhibitors and NMDA antagonists, do not halt its progression. AD and other dementias present unique pathological features such as that of microtubule associated protein tau metabolic regulation. Tau has numerous binding partners, including signaling molecules, cytoskeletal elements and lipids, which suggests that it is a multifunctional protein. AD has also been associated with severe loss of cholinergic markers in the brain and such loss may be due to the toxic interaction of tau with cholinergic muscarinic receptors. By using specific antagonists of muscarinic receptors it was found in vitro that extracellular tau binds to M1 and M3 receptors and which the increase of intracellular calcium found in neuronal cells upon tau-binding. However, so far, the significance of tau signaling through muscarinic receptor in vivo in tauopathic models remains uncertain. The data reviewed in the present paper highlight the significant effect of M1 receptor/tau interaction in exacerbating tauopathy related pathological features and suggest that selective M1 agonists may serve as a prototype for future therapeutic development toward modification of currently intractable neurodegenerative diseases, such as tauopathies.
| S-EPMC7509759 | biostudies-literature
Project description:The prevalence of neurodegenerative disease (ND) is increasing, partly owing to extensions in lifespan, with a larger percentage of members living to an older age, but the ND aetiology and pathogenesis are not fully understood, and effective treatments are still lacking. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are generally thought to progress as a consequence of genetic susceptibility and environmental influences. Up to now, several environmental triggers have been associated with NDs, and recent studies suggest that some cyanotoxins, produced by cyanobacteria and acting through a variety of molecular mechanisms, are highly neurotoxic, although their roles in neuropathy and particularly in NDs are still controversial. In this review, we summarize the most relevant and recent evidence that points at cyanotoxins as environmental triggers in NDs development.
| S-EPMC8395864 | biostudies-literature
Project description:A common biologic property of the gammaherpesviruses Epstein-Barr Virus and Kaposi sarcoma herpesvirus is their use of B lymphocytes as a reservoir of latency in healthy individuals that can undergo oncogenic transformation later in life. Gammaherpesviruses (GHVs) employ an impressive arsenal of proteins and non-coding RNAs to reprogram lymphocytes for proliferative expansion. Within lymphoid tissues, the germinal center (GC) reaction is a hub of B cell proliferation and death. The goal of a GC is to generate and then select for a pool of immunoglobulin (Ig) genes that will provide a protective humoral adaptive immune response. B cells infected with GHVs are detected in GCs and bear the hallmark signatures of the mutagenic processes of somatic hypermutation and isotype class switching of the Ig genes. However, data also supports extrafollicular B cells as a reservoir engaged by GHVs. Next-generation sequencing technologies provide unprecedented detail of the Ig sequence that informs the natural history of infection at the single cell level. Here, we review recent reports from human and murine GHV systems that identify striking differences in the immunoglobulin repertoire of infected B cells compared to their uninfected counterparts. Implications for virus biology, GHV-associated cancers, and host immune dysfunction will be discussed.
| S-EPMC7472090 | biostudies-literature
Project description:Autophagy is a fundamental cellular homeostasis mechanism known to play multifaceted roles in the natural history of cancers over time. It has recently been shown that autophagy also mediates the crosstalk between the tumor and its microenvironment by promoting the export of molecular payloads such as non-coding RNA (ncRNAs) via LC3-dependent Extracellular Vesicle loading and secretion (LDELS). In turn, the dynamic exchange of exosomal ncRNAs regulate autophagic responses in the recipient cells within the tumor microenvironment (TME), for both tumor and stromal cells. Autophagy-dependent phenotypic changes in the recipient cells further enhance tumor growth and metastasis, through diverse biological processes, including nutrient supplementation, immune evasion, angiogenesis, and therapeutic resistance. In this review, we discuss how the feedforward autophagy-ncRNA axis orchestrates vital communications between various cell types within the TME ecosystem to promote cancer progression.
| S-EPMC8750064 | biostudies-literature
Project description:Glucocorticoid-dependent mechanisms of inflammation-mediated distant hippocampal damage are discussed with a focus on the consequences of traumatic brain injury. The effects of glucocorticoids on specific neuronal populations in the hippocampus depend on their concentration, duration of exposure and cell type. Previous stress and elevated level of glucocorticoids prior to pro-inflammatory impact, as well as long-term though moderate elevation of glucocorticoids, may inflate pro-inflammatory effects. Glucocorticoid-mediated long-lasting neuronal circuit changes in the hippocampus after brain trauma are involved in late post-traumatic pathology development, such as epilepsy, depression and cognitive impairment. Complex and diverse actions of the hypothalamic-pituitary-adrenal axis on neuroinflammation may be essential for late post-traumatic pathology. These mechanisms are applicable to remote hippocampal damage occurring after other types of focal brain damage (stroke, epilepsy) or central nervous system diseases without obvious focal injury. Thus, the liaisons of excessive glucocorticoids/dysfunctional hypothalamic-pituitary-adrenal axis with neuroinflammation, dangerous to the hippocampus, may be crucial to distant hippocampal damage in many brain diseases. Taking into account that the hippocampus controls both the cognitive functions and the emotional state, further research on potential links between glucocorticoid signaling and inflammatory processes in the brain and respective mechanisms is vital.
| S-EPMC9138485 | biostudies-literature
Project description:While much evidence suggests that type 2 diabetes mellitus increases the risk of Parkinson's disease (PD), the relationship between type 1 diabetes mellitus (T1DM) and PD is unclear. To study their association, we performed a two-sample Mendelian randomization (MR) using the following statistical methods: inverse variance weighting (IVW), MR-Egger, weight median, and weighted mode. Independent datasets with no sample overlap were retrieved from the IEU GWAS platform. All the MR methods found a lower risk of PD in T1DM (IVW-OR 0.93, 95% CI 0.91-0.96, p = 3.12 × 10-5; MR-Egger-OR 0.93, 95% CI 0.88-0.98, p = 1.45 × 10-2; weighted median-OR 0.93, 95% CI 0.89-0.98, p = 2.76 × 10-3; and weighted mode-OR 0.94, 95% CI 0.9-0.98, p = 1.58 × 10-2). The findings were then replicated with another independent GWAS dataset on T1DM (IVW-OR 0.97, 95% CI 0.95-0.99, p = 3.10 × 10-3; MR-Egger-OR 0.96, 95% CI 0.93-0.99, p = 1.08 × 10-2; weighted median-OR 0.97, 95% CI 0.94-0.99, p = 1.88 × 10-2; weighted mode-OR 0.97, 95% CI 0.94-0.99, p = 1.43 × 10-2). Thus, our study provides evidence that T1DM may have a protective effect on PD risk, though further studies are needed to clarify the underlying mechanisms.
| S-EPMC10816052 | biostudies-literature
Project description:BackgroundPrevious studies showed inconsistent results regarding associations between diabetes mellitus (DM) and risk of Parkinson's disease (PD). The study aimed to make a meta-analysis to clarify whether DM is a risk factor for PD.MethodsWe searched for articles regarding the effect of DM on risk of PD and published before July 2020 with search terms as follows: ("diabetes mellitus" OR "diabetes") AND ("Parkinson's disease" OR "PD") in the following databases: PubMed, Web of Science, MEDLINE, EMBASE, and Google Scholar. We used STATA 12.0 software to compute multivariate odds ratio (OR) or relative risk (RR) and 95% confidence intervals (CI) regarding the association between DM and risk of PD.ResultsThe present study finally included 7 case-control studies (including 26,654 PD patients) and 9 cohort studies (including 3,819,006 DM patients) exploring the association between DM and risk of PD. The meta-analysis indicated that DM was related to elevated risk of PD (OR/RR = 1.15, 95% CI 1.03-1.28, I2 = 92.4%, p < .001). Subgroup study showed that DM was associated with higher risk of PD in cohort studies (RR = 1.29, 95% CI 1.15-1.45, I2 = 93.9%, p < .001), whereas no significant association was indicated between DM and risk of PD in case-control studies (OR = 0.74, 95% CI 0.51-1.09, I2 = 82.3%, p < .001). Sensitivity analysis showed no changes in the direction of effect when any one study was excluded from all meta-analyses. In addition, Begg's test, Egger's test, and funnel plot showed no significant risks of publication bias.ConclusionIn conclusion, we have tried to determine whether prior onset of DM may contribute to the risk of developing PD. More and more large-scale prospective studies should be conducted to evaluate the relationship between DM and PD.
| S-EPMC8413776 | biostudies-literature
Project description:Diabetes mellitus (DM) and Parkinson's disease (PD) are both age-related diseases of global concern being among the most common chronic metabolic and neurodegenerative diseases, respectively. While both diseases can be genetically inherited, environmental factors play a vital role in their pathogenesis. Moreover, DM and PD have common underlying molecular mechanisms, such as misfolded protein aggregation, mitochondrial dysfunction, oxidative stress, chronic inflammation, and microbial dysbiosis. Recently, epidemiological and experimental studies have reported that DM affects the incidence and progression of PD. Moreover, certain antidiabetic drugs have been proven to decrease the risk of PD and delay its progression. In this review, we elucidate the epidemiological and pathophysiological association between DM and PD and summarize the antidiabetic drugs used in animal models and clinical trials of PD, which may provide reference for the clinical translation of antidiabetic drugs in PD treatment.
| S-EPMC9662283 | biostudies-literature
Project description:Although increasing evidence has suggested crosstalk between Parkinson's disease (PD) and type 2 diabetes mellitus (T2DM), the common mechanisms between the two diseases remain unclear. The aim of our study was to characterize the interconnection between T2DM and PD by exploring their shared biological pathways and convergent molecules. The intersections among the differentially expressed genes (DEGs) in the T2DM dataset GSE95849 and PD dataset GSE6613 from the Gene Expression Omnibus (GEO) database were identified as the communal DEGs between the two diseases. Then, an enrichment analysis, protein-protein interaction (PPI) network analysis, correlation analysis, and transcription factor-target regulatory network analysis were performed for the communal DEGs. As a result, 113 communal DEGs were found between PD and T2DM. They were enriched in lipid metabolism, including protein modifications that regulate metabolism, lipid synthesis and decomposition, and the biological effects of lipid products. All these pathways and their biological processes play important roles in both diseases. Fifteen hub genes identified from the PPI network could be core molecules. Their function annotations also focused on lipid metabolism. According to the correlation analysis and the regulatory network analysis based on the 15 hub genes, Sp1 transcription factor (SP1) could be a key molecule since it affected other hub genes that participate in the common mechanisms between PD and T2DM. In conclusion, our analyses reveal that changes in lipid metabolism could be a key intersection between PD and T2DM, and that SP1 could be a key molecule regulating these processes. Our findings provide novel points for the association between PD and T2DM.
| S-EPMC7378658 | biostudies-literature
Project description:BackgroundObservational studies have indicated an association between diabetes mellitus (DM), glycemic traits, and the occurrence of Parkinson's disease (PD). However, the complex interactions between these factors and the presence of a causal relationship remain unclear. Therefore, we aim to systematically assess the causal relationship between diabetes, glycemic traits, and PD onset, risk, and progression.MethodWe used two-sample Mendelian randomization (MR) to investigate potential associations between diabetes, glycemic traits, and PD. We used summary statistics from genome-wide association studies (GWAS). In addition, we employed multivariable Mendelian randomization to evaluate the mediating effects of anti-diabetic medications on the relationship between diabetes, glycemic traits, and PD. To ensure the robustness of our findings, we performed a series of sensitivity analyses.ResultsIn our univariable Mendelian randomization (MR) analysis, we found evidence of a causal relationship between genetic susceptibility to type 1 diabetes (T1DM) and a reduced risk of PD (OR = 0.9708; 95% CI: 0.9466, 0.9956; P = 0.0214). In our multivariable MR analysis, after considering the conditions of anti-diabetic drug use, this correlation disappeared with adjustment for potential mediators, including anti-diabetic medications, insulin use, and metformin use.ConclusionOur MR study confirms a potential protective causal relationship between genetically predicted type 1 diabetes and reduced risk of PD, which may be mediated by factors related to anti-diabetic medications.
| S-EPMC10913216 | biostudies-literature