scholarly journals Metformin Repurposing for Parkinson Disease Therapy: Opportunities and Challenges

2021 ◽  
Vol 23 (1) ◽  
pp. 398
Author(s):  
Francesco Agostini ◽  
Anna Masato ◽  
Luigi Bubacco ◽  
Marco Bisaglia
Keyword(s):  
Parkinson Disease ◽  
Neurodegenerative Disorder ◽  
Low Cost ◽  
Epidemiological Studies ◽  
Experimental Models ◽  
Diabetic Patients ◽  
Motor Disabilities ◽  
Mitochondrial Functions ◽  
Disease Therapy ◽  
Disease Modifier

Parkinson disease (PD) is a severe neurodegenerative disorder that affects around 2% of the population over 65 years old. It is characterized by the progressive loss of nigrostriatal dopaminergic neurons, resulting in motor disabilities of the patients. At present, only symptomatic cures are available, without suppressing disease progression. In this frame, the anti-diabetic drug metformin has been investigated as a potential disease modifier for PD, being a low-cost and generally well-tolerated medication, which has been successfully used for decades in the treatment of type 2 diabetes mellitus. Despite the precise mechanisms of action of metformin being not fully elucidated, the drug has been known to influence many cellular pathways that are associated with PD pathology. In this review, we present the evidence in the literature supporting the neuroprotective role of metformin, i.e., autophagy upregulation, degradation of pathological α-synuclein species, and regulation of mitochondrial functions. The epidemiological studies conducted in diabetic patients under metformin therapy aimed at evaluating the correlation between long-term metformin consumption and the risk of developing PD are also discussed. Finally, we provide an interpretation for the controversial results obtained both in experimental models and in clinical studies, thus providing a possible rationale for future investigations for the repositioning of metformin for PD therapy.

scholarly journals A subacute model of glaucoma based on limbal plexus cautery in pigmented rats

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rafael Lani ◽  
Mariana S. Dias ◽  
Carla Andreia Abreu ◽  
Victor G. Araújo ◽  
Thais Gonçalo ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Retinal Ganglion Cells ◽  
Neurodegenerative Disorder ◽  
Ganglion Cells ◽  
Low Cost ◽  
Experimental Models ◽  
Learning Curves ◽  
Retinal Ganglion ◽  
Simple Method ◽  
Functional Changes

Abstract Glaucoma is a neurodegenerative disorder characterized by the progressive functional impairment and degeneration of the retinal ganglion cells (RGCs) and their axons, and is the leading cause of irreversible blindness worldwide. Current management of glaucoma is based on reduction of high intraocular pressure (IOP), one of its most consistent risk factors, but the disease proceeds in almost half of the patients despite such treatments. Several experimental models of glaucoma have been developed in rodents, most of which present shortcomings such as high surgical invasiveness, slow learning curves, damage to the transparency of the optic media which prevents adequate functional assessment, and variable results. Here we describe a novel and simple method to induce ocular hypertension in pigmented rats, based on low-temperature cauterization of the whole circumference of the limbal vascular plexus, a major component of aqueous humor drainage and easily accessible for surgical procedures. This simple, low-cost and efficient method produced a reproducible subacute ocular hypertension with full clinical recovery, followed by a steady loss of retinal ganglion cells and optic axons, accompanied by functional changes detected both by electrophysiological and behavioral methods.

scholarly journals Screening Strategy of Pancreatic Cancer in Patients with Diabetes Mellitus

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 572
Author(s):  
Suguru Mizuno ◽  
Yousuke Nakai ◽  
Kazunaga Ishigaki ◽  
Kei Saito ◽  
Hiroki Oyama ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Pancreatic Cancer ◽  
Epidemiological Studies ◽  
Screening Strategy ◽  
Diabetic Patients ◽  
Reverse Causality ◽  
Pilot Studies ◽  
Patients With Diabetes ◽  
High Risk Populations ◽  
New Onset

The incidence of pancreatic cancer (PCa) is increasing worldwide and has become one of the leading causes of cancer-related death. Screening for high risk populations is fundamental to overcome this intractable malignancy. Diabetes mellitus (DM) is classically known as a risk factor for PCa. Recently the reverse causality is in the spotlight, that is to say, DM is considered to be a manifestation of PCa. Numbers of epidemiological studies clarified that new-onset DM (≤2-year duration) was predominant in PCa patients and the relative risk for PCa inversely correlated with duration of DM. Among patients with new-onset DM, elder onset, weight loss, and rapid exacerbation of glycemic control were reported to be promising risk factors and signs, and the model was developed by combining these factors. Several pilot studies disclosed the possible utility of biomarkers to discriminate PCa-associated DM from type 2 DM. However, there is no reliable biomarkers to be used in the practice. We previously reported the application of a multivariate index for PCa based on the profile of plasma free amino acids (PFAAs) among diabetic patients. We are further investigating on the PFAA profile of PCa-associated DM, and it can be useful for developing the novel biomarker in the near future.

The Utilization of Mobile Applications for Self-Care in People With Parkinson Disease: Systematic Review (Preprint)

2021 ◽  
Author(s):  
JuHee Hee ◽  
Insun Yeom ◽  
Misook Lee Chung ◽  
Yielin Kim ◽  
Subin Yoo ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Task Performance ◽  
Systematic Reviews ◽  
Mobile Applications ◽  
Symptom Management ◽  
Neurodegenerative Disorder ◽  
Self Care ◽  
Cochrane Library ◽  
Symptom Improvement ◽  
Motor Symptoms

BACKGROUND Self-care is essential for people with Parkinson disease (PD) to minimize their disability and adapt to alterations in physical abilities due to progressive neurodegenerative disorder. With rapid developments in mobile technology, many health-related mobile applications for PD have been developed and utilized. However, insufficient research has investigated mobile application-based self-care in PD. OBJECTIVE This study aimed to explore the features and characteristics of the utilization of mobile applications for self-care in people with PD. METHODS This study was performed sequentially according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Referred databases are PubMed, Embase, CINAHL, Cochrane Library, Web of Science and PsycINFO in consultation with a librarian on June 8, 2021. We used keywords including ‘Parkinson disease’ and ‘mobile.’ RESULTS A total of 17 studies were selected by the inclusion criteria, including 3 randomized controlled trials and 14 observational studies/quasi-experimental studies. The utilization of mobile applications for self-care in people with PD focused on symptom monitoring, especially tracking motor symptoms. Motor symptoms were objectively measured mainly through the sensors of smartphones or wearable devices and task performance. Non-motor symptoms were monitored through task performance or self-reported questionnaires in mobile applications. Most studies focused on clinical symptom assessment in people with PD, and there was a lack of studies focusing on symptom management. CONCLUSIONS Mobile applications for people with PD have been developed and utilized, but strategies for self-management are insufficient. We recommend the development of mobile applications focused on self-care that can enhance symptom management and health promotion practices. Studies should also evaluate the effects of mobile applications on symptom improvement and quality of life in people with PD. CLINICALTRIAL PROSPERO International Prospective Register of Systematic Reviews CRD42021267374.

scholarly journals A comparison of resting state EEG and structural MRI for classifying Alzheimer’s disease and mild cognitive impairment

2019 ◽  
Author(s):  
FR Farina ◽  
DD Emek-Savaş ◽  
L Rueda-Delgado ◽  
R Boyle ◽  
H Kiiski ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Resting State ◽  
Healthy Aging ◽  
Neurodegenerative Disorder ◽  
Low Cost ◽  
Structural Mri ◽  
Lower Accuracy

AbstractAlzheimer’s disease (AD) is a neurodegenerative disorder characterised by severe cognitive decline and loss of autonomy. AD is the leading cause of dementia. AD is preceded by mild cognitive impairment (MCI). By 2050, 68% of new dementia cases will occur in low- and middle-income countries. In the absence of objective biomarkers, psychological assessments are typically used to diagnose MCI and AD. However, these require specialist training and rely on subjective judgements. The need for low-cost, accessible and objective tools to aid AD and MCI diagnosis is therefore crucial. Electroencephalography (EEG) has potential as one such tool: it is relatively inexpensive (cf. magnetic resonance imaging; MRI) and is portable. In this study, we collected resting state EEG, structural MRI and rich neuropsychological data from older adults (55+ years) with AD, with MCI and from healthy controls (n~60 per group). Our goal was to evaluate the utility of EEG, relative to MRI, for the classification of MCI and AD. We also assessed the performance of combined EEG and behavioural (Mini-Mental State Examination; MMSE) and structural MRI classification models. Resting state EEG classified AD and HC participants with moderate accuracy (AROC=0.76), with lower accuracy when distinguishing MCI from HC participants (AROC=0.67). The addition of EEG data to MMSE scores had no additional value compared to MMSE alone. Structural MRI out-performed EEG (AD vs HC, AD vs MCI: AROCs=1.00; HC vs MCI: AROC=0.73). Resting state EEG does not appear to be a suitable tool for classifying AD. However, EEG classification accuracy was comparable to structural MRI when distinguishing MCI from healthy aging, although neither were sufficiently accurate to have clinical utility. This is the first direct comparison of EEG and MRI as classification tools in AD and MCI participants.

scholarly journals Onboard Cloud-enabled Parkinson Disease Identification System Using Enhanced Grey Wolf Optimization

Webology ◽  
2021 ◽  
Vol 18 (Special Issue 04) ◽  
pp. 1360-1372
Author(s):  
Ramaprabha Jayaram ◽  
T. Senthil Kumar
Keyword(s):  
Feature Selection ◽  
Parkinson Disease ◽  
Neurodegenerative Disorder ◽  
Feature Selection Method ◽  
Selection Method ◽  
Identification System ◽  
Grey Wolf ◽  
Grey Wolf Optimization ◽  
Time Duration ◽  
Disease Identification

Parkinson disease is a rigorous neurodegenerative disorder characterized by the cognitive behavior ending with disability problems. Especially, the elderly people should be given more care and spend more time duration to diagnose when they are at risk. It is more important to identify and diagnose Parkinson disease at an earlier stage rather than spending too much of cost later stages. Different ways of diagnosing the disease ranging from gene analysis to gait behavior, speech, writing test and olfactory models were used in the conventional testing process. In order to increase the patient’s quality of life and minimize the cost of healthcare utilization, an Onboard Cloud-Enabled Parkinson Disease Identification System (OCPDIS) is proposed. An enhanced grey wolf optimization is explored along with the differential evolution techniques to form an effective hybrid feature selection method. Using this feature selection method in the enhanced k-Nearest Neighbor (k-NN) classifier model could substantially improve the prediction time and prediction accuracy.

scholarly journals Association of SHANK3 Gene Polymorphism and Parkinson Disease in the North of Iran

2021 ◽  
Vol 12 (1) ◽  
pp. 57-62
Author(s):  
Nahid Mizban ◽  
◽  
Nasim Vousooghi ◽  
Nasrin Mizban ◽  
◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Neurodegenerative Disorder ◽  
Genotype Distribution ◽  
Scaffolding Proteins ◽  
Allele Distribution ◽  
The North ◽  
Increased Risk ◽  
Significant Difference ◽  
North Of Iran ◽  
Domain 3

Introduction: Parkinson Disease (PD), the second most common chronic neurodegenerative disorder, is characterized by tremor, bradykinesia, rigidity, and postural instability. SHANK3 (SH3 and multiple ankyrin repeat domain 3) belongs to the extremely conserved ProSAP/ Shank family of synaptic scaffolding proteins. Meanwhile, rs9616915 is a non-synonymous SNP (T>C) located in the exon 6 of the SHANK3 gene, which induces substitution of isoleucine to threonine and affects the function of the resulted protein. The present study aimed to evaluate whether rs9616915 polymorphism of SHANK3 is involved in the susceptibility to PD. Methods: The study subjects were 100 patients diagnosed with PD and 100 control volunteers. The obtained samples were evaluated by the polymerase chain reaction-restriction fragment length polymorphism method. Results: A significant association was found in genotype distribution between cases and controls. Individuals with TC genotype had increased risk of PD (P=0.035, OR=1.98, 95% CI=1.04 - 3.74). No significant difference was found in allele distribution (P=0.7). Conclusion: The findings suggest that the SHANK3 rs9616915 polymorphism is associated with an increased risk of PD in the population. Further studies are needed to confirm the role of the SHANK3 gene in PD.

scholarly journals The Rotenone Models Reproducing Central and Peripheral Features of Parkinson’s Disease

NeuroSci ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 1-14
Author(s):  
Ikuko Miyazaki ◽  
Masato Asanuma
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Neurodegenerative Disorder ◽  
Rem Sleep Behavior Disorder ◽  
Experimental Models ◽  
Motor Symptoms ◽  
Sleep Behavior ◽  
Disease Modifying Drugs

Parkinson’s disease (PD) is a complex, multi-system, neurodegenerative disorder; PD patients exhibit motor symptoms (such as akinesia/bradykinesia, tremor, rigidity, and postural instability) due to a loss of nigrostriatal dopaminergic neurons, and non-motor symptoms such as hyposmia, autonomic disturbance, depression, and REM sleep behavior disorder (RBD), which precedes motor symptoms. Pathologically, α-synuclein deposition is observed in the central and peripheral nervous system of sporadic PD patients. To clarify the mechanism of neurodegeneration in PD and to develop treatment to slow or stop PD progression, there is a great need for experimental models which reproduce neurological features of PD. Animal models exposed to rotenone, a commonly used pesticide, have received most attention since Greenamyre and his colleagues reported that chronic exposure to rotenone could reproduce the anatomical, neurochemical, behavioral, and neuropathological features of PD. In addition, recent studies demonstrated that rotenone induced neuropathological change not only in the central nervous system but also in the peripheral nervous system in animals. In this article, we review rotenone models especially focused on reproducibility of central and peripheral multiple features of PD. This review also highlights utility of rotenone models for investigation of PD pathogenesis and development of disease-modifying drugs for PD in future.

Sign in / Sign up

Export Citation Format

Share Document