scholarly journals Beneficial Effects of Metformin on the Central Nervous System, with a Focus on Epilepsy and Lafora Disease

2021 ◽  
Vol 22 (10) ◽  
pp. 5351
Author(s):  
Pascual Sanz ◽  
José Maria Serratosa ◽  
Marina P. Sánchez
Keyword(s):  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Special Focus ◽  
Lafora Disease ◽  
Beneficial Effects ◽  
Progressive Myoclonus Epilepsy ◽  
The Family ◽  
Myoclonus Epilepsy ◽  
The Central Nervous System

Metformin is a drug in the family of biguanide compounds that is widely used in the treatment of type 2 diabetes (T2D). Interestingly, the therapeutic potential of metformin expands its prescribed use as an anti-diabetic drug. In this sense, it has been described that metformin administration has beneficial effects on different neurological conditions. In this work, we review the beneficial effects of this drug as a neuroprotective agent in different neurological diseases, with a special focus on epileptic disorders and Lafora disease, a particular type of progressive myoclonus epilepsy. In addition, we review the different proposed mechanisms of action of metformin to understand its function at the neurological level.

Role of the glucose-dependent insulinotropic polypeptide and its receptor in the central nervous system: therapeutic potential in neurological diseases

2010 ◽  
Vol 21 (5-6) ◽  
pp. 394-408 ◽  
Author(s):  
Cláudia P. Figueiredo ◽  
Fabrício A. Pamplona ◽  
Tânia L. Mazzuco ◽  
Aderbal S. Aguiar ◽  
Roger Walz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
The Central Nervous System

scholarly journals Gys1 antisense therapy rescues neuropathological bases of murine Lafora disease

2021 ◽  
Author(s):  
Saija Ahonen ◽  
Silvia Nitschke ◽  
Tamar R. Grossman ◽  
Holly Kordasiewicz ◽  
Peixiang Wang ◽  
...  
Keyword(s):  
Antisense Oligonucleotide ◽  
Glycogen Synthase ◽  
Lafora Disease ◽  
Neuroinflammatory Response ◽  
Glycogen Accumulation ◽  
Body Formation ◽  
Lafora Bodies ◽  
Progressive Myoclonus Epilepsy ◽  
Myoclonus Epilepsy ◽  
Lafora Body

AbstractLafora disease is a fatal progressive myoclonus epilepsy. At root, it is due to constant acquisition of branches that are too long in a subgroup of glycogen molecules, leading them to precipitate and accumulate into Lafora bodies, which drive a neuroinflammatory response and neurodegeneration. As a potential therapy, we aimed to downregulate glycogen synthase, the enzyme responsible for glycogen branch elongation, in the disease’s mouse models. We synthesized an antisense oligonucleotide (Gys1-ASO) that targets the mRNA of the brain-expressed glycogen synthase 1 gene (Gys1). We administered Gys1-ASO by intracerebroventricular injection and analyzed the pathological hallmarks of Lafora disease, namely glycogen accumulation, Lafora body formation, and neuroinflammation. Gys1-ASO prevented Lafora body formation in young mice that had not yet formed them. In older mice that already exhibited Lafora bodies, Gys1-ASO inhibited further accumulation, markedly preventing large Lafora bodies characteristic of advanced disease. Inhibition of Lafora body formation was associated with prevention of astrogliosis and strong trends towards correction of dysregulated expression of disease immune and neuroinflammatory markers. Lafora disease manifests gradually in previously healthy teenagers. Our work provides proof of principle that an antisense oligonucleotide targeting the GYS1 mRNA could prevent, and halt progression of, this catastrophic epilepsy.

scholarly journals Is adjunctive perampanel beneficial for lafora disease?

2020 ◽  
Vol 77 (5) ◽  
pp. 539-544
Author(s):  
Galina Stevanovic ◽  
Nebojsa Jovic ◽  
Miljana Kecmanovic
Keyword(s):  
Case Studies ◽  
Functional Disability ◽  
Single Case ◽  
Case Series ◽  
Lafora Disease ◽  
Open Label ◽  
Progressive Myoclonus Epilepsy ◽  
Case Series Study ◽  
Myoclonus Epilepsy ◽  
Psychiatric Side Effects

Backgrund/Aim. Lafora disease (LD) is progressive myoclonus epilepsy, characterized by intractable myoclonus and seizures, inevitable neurological deterioration, brutal cognitive decline and poor prognosis. The treatment still remains purely symptomatic. Recently, two single-case studies and one case series study reported the favourable effects of perampanel in LD. Our study aimed to test the benefits reported in three separate case studies. Methods. We performed an open label, prospective study of 4 patients aged between 22 and 34 years with mutation in NHLRC1 (EPM2B) gene, treated with perampanel (6?8 mg/day) as add-on therapy. Follow-up period comprised 14?26 months. Seizure frequency, myoclonus, functional disability and cognitive performance were analysed. Results. In 3 patients, both, seizures and myoclonus, showed remarkable improvement after the drug introduction (> 50% reduction). No significant effect was seen in one case. The functional and cognitive impairment maintained at the same level, though all patients were at the later stage of the disease. Psychiatric side effects were dose related. Conclusion. Our study supports the rare, previously reported observations that perampanel is beneficial in treating LD patients.

scholarly journals Progressive Myoclonus Epilepsy in Congenital Generalized Lipodystrophy type 2: Report of 3 cases and literature review

Seizure ◽  
2016 ◽  
Vol 42 ◽  
pp. 1-6 ◽  
Author(s):  
Roberta Opri ◽  
Gian Maria Fabrizi ◽  
Gaetano Cantalupo ◽  
Moreno Ferrarini ◽  
Alessandro Simonati ◽  
...  
Keyword(s):  
Literature Review ◽  
Congenital Generalized Lipodystrophy ◽  
Progressive Myoclonus Epilepsy ◽  
Myoclonus Epilepsy

Lafora disease: A progressive myoclonus epilepsy

1992 ◽  
Vol 28 (6) ◽  
pp. 455-458 ◽  
Author(s):  
E. J. ELLIOTT ◽  
I. C. TALBOT ◽  
I. F. PYE ◽  
S. HODGES ◽  
P. G. F. SWIFT ◽  
...  
Keyword(s):  
Lafora Disease ◽  
Progressive Myoclonus Epilepsy ◽  
Myoclonus Epilepsy

scholarly journals Recent Advances in Studies on the Therapeutic Potential of Dietary Carotenoids in Neurodegenerative Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Kyoung Sang Cho ◽  
Myeongcheol Shin ◽  
Sunhong Kim ◽  
Sung Bae Lee
Keyword(s):  
Neurodegenerative Diseases ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Natural Pigment ◽  
Protective Function ◽  
Characteristic Structure ◽  
Model Studies ◽  
Beneficial Effects ◽  
Treatment And Prevention ◽  
Bioactive Properties

Carotenoids, symmetrical tetraterpenes with a linear C40 hydrocarbon backbone, are natural pigment molecules produced by plants, algae, and fungi. Carotenoids have important functions in the organisms (including animals) that obtain them from food. Due to their characteristic structure, carotenoids have bioactive properties, such as antioxidant, anti-inflammatory, and autophagy-modulatory activities. Given the protective function of carotenoids, their levels in the human body have been significantly associated with the treatment and prevention of various diseases, including neurodegenerative diseases. In this paper, we review the latest studies on the effects of carotenoids on neurodegenerative diseases in humans. Furthermore, animal and cellular model studies on the beneficial effects of carotenoids on neurodegeneration are also reviewed. Finally, we discuss the possible mechanisms and limitations of carotenoids in the treatment and prevention of neurological diseases.

Progressive Myoclonus Epilepsy Type 2

2009 ◽  
pp. 1724-1724
Author(s):  
Markus Braun-Falco ◽  
Henry J. Mankin ◽  
Sharon L. Wenger ◽  
Markus Braun-Falco ◽  
Stephan DiSean Kendall ◽  
...  
Keyword(s):  
Progressive Myoclonus Epilepsy ◽  
Myoclonus Epilepsy

scholarly journals Angiotensin II type 2 receptor ligand PD123319 attenuates hyperoxia-induced lung and heart injury at a low dose in newborn rats

2014 ◽  
Vol 307 (3) ◽  
pp. L261-L272 ◽  
Author(s):  
Gerry T. M. Wagenaar ◽  
Rozemarijn M. A. Sengers ◽  
El Houari Laghmani ◽  
Xueyu Chen ◽  
Melissa P. H. A. Lindeboom ◽  
...  
Keyword(s):  
Early Treatment ◽  
Therapeutic Potential ◽  
Recovery Period ◽  
Continuous Exposure ◽  
Treatment Model ◽  
Newborn Rats ◽  
Beneficial Effects ◽  
Collagen Iii ◽  
Late Treatment

Intervening in angiotensin (Ang)-II type 2 receptor (AT2) signaling may have therapeutic potential for bronchopulmonary dysplasia (BPD) by attenuating lung inflammation and preventing arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH). We first investigated the role of AT2 inhibition with PD123319 (0.5 and 2 mg·kg−1·day−1) on the beneficial effect of AT2 agonist LP2–3 (5 μg/kg twice a day) on RVH in newborn rats with hyperoxia-induced BPD. Next we determined the cardiopulmonary effects of PD123319 (0.1 mg·kg−1·day−1) in two models: early treatment during continuous exposure to hyperoxia for 10 days and late treatment starting on day 6 in rat pups exposed postnatally to hyperoxia for 9 days, followed by a 9-day recovery period in room air. Parameters investigated included lung and heart histopathology, fibrin deposition, vascular leakage, and differential mRNA expression. Ten days of coadministration of LP2–3 and PD123319 abolished the beneficial effects of LP2–3 on RVH in experimental BPD. In the early treatment model PD123319 attenuated cardiopulmonary injury by reducing alveolar septal thickness, pulmonary influx of inflammatory cells, including macrophages and neutrophils, medial wall thickness of small arterioles, and extravascular collagen III deposition, and by preventing RVH. In the late treatment model PD123319 diminished PAH and RVH, demonstrating that PAH is reversible in the neonatal period. At high concentrations PD123319 blocks the beneficial effects of the AT2-agonist LP2–3 on RVH. At low concentrations PD123319 attenuates cardiopulmonary injury by reducing pulmonary inflammation and fibrosis and preventing PAH-induced RVH but does not affect alveolar and vascular development in newborn rats with experimental BPD.

scholarly journals Re-Examining the Role of TNF in MS Pathogenesis and Therapy

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2290 ◽  
Author(s):  
Diego Fresegna ◽  
Silvia Bullitta ◽  
Alessandra Musella ◽  
Francesca Romana Rizzo ◽  
Francesca De Vito ◽  
...  
Keyword(s):  
Neurological Disorder ◽  
Experimental Studies ◽  
Convincing Evidence ◽  
Special Focus ◽  
Pathophysiological Role ◽  
The Central Nervous System ◽  
Ms Pathogenesis

Multiple sclerosis (MS) is a common neurological disorder of putative autoimmune origin. Clinical and experimental studies delineate abnormal expression of specific cytokines over the course of the disease. One major cytokine that has been shown to play a pivotal role in MS is tumor necrosis factor (TNF). TNF is a pleiotropic cytokine regulating many physiological and pathological functions of both the immune system and the central nervous system (CNS). Convincing evidence from studies in human and experimental MS have demonstrated the involvement of TNF in various pathological hallmarks of MS, including immune dysregulation, demyelination, synaptopathy and neuroinflammation. However, due to the complexity of TNF signaling, which includes two-ligands (soluble and transmembrane TNF) and two receptors, namely TNF receptor type-1 (TNFR1) and type-2 (TNFR2), and due to its cell- and context-differential expression, targeting the TNF system in MS is an ongoing challenge. This review summarizes the evidence on the pathophysiological role of TNF in MS and in different MS animal models, with a special focus on pharmacological treatment aimed at controlling the dysregulated TNF signaling in this neurological disorder.

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