Shared dysregulated pathways lead to Parkinson's disease and diabetes

Santiago, José A.; Potashkin, Judith A.

doi:10.1016/j.molmed.2013.01.002

Cited by 202 publications

(176 citation statements)

References 122 publications

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“…Several recent discoveries have highlighted common cellular pathways that potentially relate neurodegenerative processes with abnormal mitochondrial function and abnormal glucose metabolism [2]. In parallel with these advances, a treatment for insulin resistance (exenatide; a GLP-1 agonist) has been proposed as a disease modifying drug in PD, based on multiple in vitro and in vivo studies [3][4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Motor and Cognitive Advantages Persist 12 Months After Exenatide Exposure in Parkinson’s Disease

Avilés-Olmos

Dickson

Kefalopoulou

et al. 2014

JPD

228

148

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Abstract. Background:Data from an open label randomised controlled trial have suggested possible advantages on both motor and non-motor measures in patients with Parkinson's disease following 12 months exposure to exenatide. Objective: Continued follow up of these same patients was performed to investigate whether these possible advantages persisted in the prolonged absence of this medication. Methods: All participants from an open label, randomised controlled trial of exenatide as a treatment for Parkinson's disease, were invited for a further follow up assessment at the UCL Institute of Neurology. This visit included all 20 individuals who had previously completed twelve months exposure to exenatide 10ug bd and the 24 individuals who had acted as randomised controls. Motor severity of PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the MDS-UPDRS, together with several non-motor tests. This assessment was thus 24 months after their original baseline visit, i.e. 12 months after cessation of exenatide. Results: Compared to the control group of patients, patients previously exposed to exenatide had an advantage of 5.6 points (95% CI, 2.2-9.0; p = 0.002) using blinded video rating of the MDS-UPDRS part 3 motor subscale. There was also a difference of 5.3 points; (95% CI, 9.3-1.4; p = 0.006) between the 2 groups on the Mattis Dementia Rating scale.

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Section: Introductionmentioning

confidence: 99%

Motor and Cognitive Advantages Persist 12 Months After Exenatide Exposure in Parkinson’s Disease

Avilés-Olmos

Dickson

Kefalopoulou

et al. 2014

JPD

228

148

View full text Add to dashboard Cite

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“…One study has shown that PD patients had diabetes mellitus (DM) and heart diseases as frequently as in the general population and these illnesses are common irrespective of gender or race 16 . Many studies suggest the asso-ciation of DM with PD because both are agerelated chronic diseases and share remarkably similar pathways of mitochondrial dysfunction 17,18 .…”

Section: Discussionmentioning

confidence: 99%

Comparative study of clinical profile between familial and sporadic Parkinson's disease

Jukkarwala¹

2017

J Med Allied Sci

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“…More recently, cerebrospinal fluid (CSF) concentrations of Ab peptides have been widely used to study Alzheimer's disease pathology in vivo and their utility to diagnose Parkinson's disease with dementia is under evaluation [32]. In addition to Alzheimer's disease, other neurological disorders including Down's syndrome, autism, and epilepsy are characterized by elevated expression of APP [33].…”

Section: Discussionmentioning

confidence: 99%

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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Shared dysregulated pathways lead to Parkinson's disease and diabetes

Cited by 202 publications

References 122 publications

Motor and Cognitive Advantages Persist 12 Months After Exenatide Exposure in Parkinson’s Disease

Motor and Cognitive Advantages Persist 12 Months After Exenatide Exposure in Parkinson’s Disease

Comparative study of clinical profile between familial and sporadic Parkinson's disease

Splice Variant Biomarkers for Parkinson's Disease

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