Dementia is associated with Insulin Resistance in patients with Parkinson's Disease

Bosco, Domenico; Plastino, Massimiliano; Cristiano, Dario; Colica, Carmela; Ermio, Caterina; Bartolo, Matteo De; Mungari, Pasquale; Fonte, Giulia; Consoli, Domenico; Consoli, Arturo; Fava, Antonietta

doi:10.1016/j.jns.2011.12.008

Cited by 128 publications

(94 citation statements)

References 36 publications

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Section: Epidemiological and Clinical Studies In Pd And T2dmmentioning

confidence: 78%

“…Not surprisingly, repeated inpatient care and longer duration of hospitalization is observed in PD patients with T2DM (Scheuing et al, 2013). Insulin resistance, a hallmark feature of T2DM, is associated with an increased risk of dementia in PD (Bosco et al, 2012). In addition, T2DM contributes to postural instability and gait difficulty in PD .…”

Section: Epidemiological and Clinical Studies In Pd And T2dmmentioning

confidence: 99%

“…Case-control studies indicate that T2DM is associated with an increased risk of PD in some ethnic groups including Danish, Chinese and Taiwanese . Similarly, a positive association between PD and T2DM was indicated in large cohort studies and 62% of PD patients with dementia are insulin resistant Bosco et al, 2012).Notwithstanding the evidence supporting the association between PD and T2DM, there remains uncertainty given the studies that have found inverse associations (D'Amelio et al, 2009;Lu et al, 2014) or no association Savica et al, 2012).One possible factor that may explain the conflictive findings among epidemiological studies is that diagnosis of T2DM is sometimes based on self-report. Another important confounding factor is the impact of drugs used to treat patients with PD and T2DM.…”

mentioning

confidence: 99%

“…In this study, APP mRNA was found to be upregulated in blood of PD patients compared to healthy individuals (Santiago and Potashkin, 2013a)( Figure 2C). Given the role of APP in insulin regulation (Rende et al, 2013), and the prevalence of insulin resistance in PD patients (Bosco et al, 2012;, the evaluation of APP as a predictor of neurodegeneration in T2DM patients warrants further investigation. …”

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confidence: 99%

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Splice Variant Biomarkers for Parkinson's Disease

Potashkin¹

2014

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATEMay PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) PERFORMING ORGANIZATION REPORT NUMBERRosalind Franklin U. Medicine & Science 3333 Green Bay Rd. North Chicago, IL 60064-3037 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTRecently we identified splice variants in whole blood than can distinguish early stage Parkinson's disease (PD) patients from healthy and neurodegenerative controls. The proposed studies will test the hypothesis that the biomarkers will be useful for identifying individuals at risk for PD and for identifying signaling pathways that are disrupted in PD. We are testing the expression of the biomarkers in RNA prepared from whole blood of hyposmic participants in the Parkinson's Associated Risk Study (PARS) (Technical Objective 1.0). In order to establish a model for testing the function of the biomarkers, we are determining whether their expression is altered in human olfactory neurosphere-derived (hONS) cells derived from idiopathic PD patients and healthy controls (Technical Objective 2.0). To determine the signaling pathways affected in PD and identify additional biomarkers, we are using network analysis (Technical Objective 3.0). During year 1, RNA and cDNA was prepared from PARS samples from Year 0 (baseline) and Year 2. Quantitative polymerase chain reactions were initiated for two of the biomarkers (APP, HNF4α). Expression of the biomarkers was tested in hONS. We also developed network approaches to reveal the common molecular pathways involved with PD and type 2 diabetes (T2DM). Using these networks, we identified APP, HNF4A and SOD2 mRNAs as blood biomarkers predictive of early stage PD. In addition, we determined that HNF4A mRNA may be a progression marker in blood for PD. SUBJECT TERMSParkinson's disease, biomarkers, neurodegeneration, network and pathway analysis 12-15Santiago 16-23Sei...

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Section: Epidemiological and Clinical Studies In Pd And T2dmmentioning

confidence: 78%

Section: Epidemiological and Clinical Studies In Pd And T2dmmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Splice Variant Biomarkers for Parkinson's Disease

Potashkin¹

2014

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“…Diabetes has been linked to cognitive impairment in both PD and Alzheimer's disease (AD) [23,24]. A case control study showed that PD patients with insulin-resistance have a two-folded increased risk of developing dementia [25]. By using positron emission tomography (PET) molecular imaging, it has been demonstrated that while there was a greater degree of cognitive impairment in PD patients with diabetes compared with PD patients without diabetes, there were no differences in nigrostriatal or cortical cholinergic PET markers [24].…”

Section: Introductionmentioning

confidence: 99%

Parkinson';s Disease, Diabetes and Cognitive Impairment

Ashraghi¹,

Pagano²,

Polychronis³

et al. 2016

EMI

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Patents published in the last 5 years could be used in novel approaches to Parkinson's treatment by targeting specific pathophysiology proteins, such as Nurr1, PINK1 and NrF2, while patents to improve penetration of the blood brain barrier could allow improved efficacy of existing treatments. Conclusion:Further studies using GLP-1 agonists and DPP-4 inhibitors to treat PD are warranted as they have shown promise.

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The GLP‐1/GIP dual‐receptor agonist DA5‐CH inhibits the NF‐κB inflammatory pathway in the MPTP mouse model of Parkinson's disease more effectively than the GLP‐1 single‐receptor agonist NLY01

Xue

Cheng

et al. 2021

Brain and Behavior

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The GLP-1 receptor agonist exendin-4 has recently shown good effects in a phase II clinical trial in Parkinson's disease (PD) patients. Here, a comparison of the new GLP-1/GIP dual receptor agonist DA5-CH and NLY01, a 40 kDa pegylated form of exendin-4, on motor impairments and reducing inflammation in the 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) PD mouse model is provided. The drug groups received either DA5-CH or NLY01 (25 nmol/kg) i.p. after daily MPTP intraperitoneal injection.Both drugs showed improvements in motor activity, open field experiments, rotarod tests, and gait analysis, but DA5-CH was more potent. Tyrosine hydroxylase expression in dopaminergic neurons was much reduced by MPTP and improved by DA5-CH, while NLY01 showed weak effects. When analyzing levels of α-synuclein (α-Syn), DA5-CH reduced levels effectively while NLY01 had no effect. When measuring the levels of the inflammation markers Toll-like receptor 4 (TLR4), specific markers of microglia activation (Iba-1), the marker of astrocyte activation glial fibrillary acidic protein (GFAP), nuclear factor-κB (NF-κB), tumor necrosis factor (TNF-α), and transforming growth factor β1 (TGF-β1), DA5-CH was very effective in reducing the chronic inflammation response, while NLY01 did not show significant effects. Levels of key growth factors such as Glial cell-derived neurotrophic factor (GDNF) and Brain-derived neurotrophic factor (BDNF) were much reduced by MPTP, and DA5-CH was able to normalize levels in the brain, while NLY01 showed little effect. The levels of pro-inflammatory cytokines (IL-6 and IL-Iβ) were much reduced by DA5-CH, too, while NLY01 showed no effect. In a separate experiment, we tested the ability of the two drugs to cross the blood-brain barrier. After injecting fluorescin-labelled peptides peripherally, the fluorescence in brain tissue was measured. It was found that the pegylated NLY01 peptide did not cross the BBB in meaningful quantities while exendin-4 and the dual agonist DA5-CH did. The results show that DA5-CH shows promise as a therapeutic drug for PD.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Dementia is associated with Insulin Resistance in patients with Parkinson's Disease

Cited by 128 publications

References 36 publications

Splice Variant Biomarkers for Parkinson's Disease

Splice Variant Biomarkers for Parkinson's Disease

Parkinson';s Disease, Diabetes and Cognitive Impairment

The GLP‐1/GIP dual‐receptor agonist DA5‐CH inhibits the NF‐κB inflammatory pathway in the MPTP mouse model of Parkinson's disease more effectively than the GLP‐1 single‐receptor agonist NLY01

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