Vol 4-1 Mini Review

Multi-Ethnic Comparison of the Characteristics of Amyotrophic Lateral Sclerosis-Related TBK1 Gene Variants

Genki Tohnai1, Ryoichi Nakamura1, Masahiro Nakatochi2, Naoki Atsuta1, Masahisa Katsuno1, Gen Sobue1,3*

1Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Statistical Analysis Section, Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan

3Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease, and the etiology of sporadic ALS is unknown. The TANK-binding kinase 1 (TBK1) gene identified as an ALS gene, contributes towards a predisposition for ALS. In this review, we analyzed variants of TBK1 found in ALS cohort studies belonging to various regions and ethnic populations. TBK1 variants tend to be enriched in patients with ALS compared to patients without ALS. The frequency of TBK1 variants is more in the familial Caucasian than that in the Asian population. However, loss of function (LoF) variant associated with sporadic ALS is almost similar among the Asian group, including Japanese population. LoF variants were frequently reported to be associated with the TBK1 biology. These findings indicate that TBK1- LoF variants are pathogenic for ALS, regardless of race or region.

DOI: 10.29245/2572.942X/2019/1.1236 View / Download Pdf View Full Text
Vol 4-1 Mini Review

Treatment of Parkinson's Disease after the Wearing Off Sets in

Yoshikuni Mizuno

Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan

In 2018, we wrote a paper on the drug treatment of Parkinson's disease. In this article, we obtained that the wearing off was observed in 77%, but the incidence of dyskinesia was 37.7% for the Parkinson?s disease patients from the onset of the disease 16-20 years. In this review article, we will discuss some of the newer treatments of Parkinson?s disease first, i.e., transplantation with induced pluripotent stem cell-derived cells, gene therapy, deep brain stimulation, levodopa/ carbidopa intrajejunal gel infusion, MRI-supported focused ultrasound, and IPX066. Then, we will discuss our opinion on the mechanism of wearing off and dyskinesia, and modifications of levodopa treatment after the wearing off sets in.

DOI: 10.29245/2572.942X/2019/1.1241 View / Download Pdf View Full Text
Vol 4-1 Mini Review

The Role of Oxidative Stress in Cocaine Addiction

Tehila Beiser, Rami Yaka*

Institute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel

Cocaine is a powerfully addictive psychostimulant that elevates dopamine (DA) levels in the mesolimbic system and causes a feeling of wellbeing. At the same time, cocaine leads to toxic effects in many essential organs, including the brain. The harmful effects of cocaine on the brain are the basis for the development of compulsive and irrational behaviors, an integral part of cocaine addiction. Over the last two decades, it has been suggested that the damage and reinforcing properties of cocaine are associated with increased reactive oxygen species (ROS) production. This increase impairs the endogenous defense antioxidant system, either directly by cocaine metabolites, or indirectly via increased DA metabolites, resulting in oxidative stress (OS). It was thus plausible to seek an exogenous, stable and non-toxic antioxidant, which can penetrate the blood brain barrier and counteract the oxidative damage in the brain caused by drugs of abuse such as cocaine. In this mini-review we describe studies that explore the role of antioxidants in reducing the OS state in the brain reward system and consequently reversing negative behavioral outcomes induced by cocaine.

DOI: 10.29245/2572.942X/2019/1.1239 View / Download Pdf View Full Text
Vol 4-1 Review Article

Amylin Signaling in Diabetes and Alzheimer's Disease: Therapy or Pathology?

John Grizzanti1, Rachel Corrigan1, Spencer Servizi1, Gemma Casadesus1,2*

1School of Biomedical Sciences, Kent State University, Ohio, USA

2Department of Biological Sciences, Kent State University, Ohio, USA

Growing evidence highlights the intimate relationship between type II diabetes (T2D) and Alzheimer’s disease (AD). Importantly, these two diseases share a number of pathological similarities, including amyloid accumulation, oxidative stress, inflammation, and cell death. To date, drug therapies for AD and T2D are lacking and there is a crucial need for the discovery and development of novel therapeutics for these diseases. A number of human and rodent studies have given evidence that metabolic hormone supplementation is highly valuable for improving cognitive function and overall metabolic health in both T2D and AD. The pancreatic hormone amylin has arisen as a crucial component of the disease etiology of both T2D and AD, though the exact role that amylin plays in these diseases is not yet well understood. Here, we critically review the current literature that utilizes human amylin or its synthetic analogue, pramlintide, as well as amylin receptor antagonists for the treatment of AD.

DOI: 10.29245/2572.942X/2019/1.1212 View / Download Pdf View Full Text
Vol 4-1 Review Article

Survival in Transthyretin Familial Amyloid Polyneuropathy: A Review

Monica Ines1, Joao Costa1,2,3*

1Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal

2Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal

3Centro de Estudos de Medicina Baseada na Evidência, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028, Lisboa, Portugal

Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a neurological disease that affects severely patients and their families and caregivers over generations. It is a rare, progressive, and if untreated fatal autosomal dominant hereditary disorder. The disease may affect multiple organ systems and if untreated progress rapidly to death. TTR-FAP affects nearly 10,000 people worldwide, with known endemic regions in Portugal, Sweden, and Japan. Until recently only liver transplantation and tafamidis were treatment options across several world regions. Despite the worldwide use of these disease-modifying treatments to delay disease progression, challenges in clinical assessment and management remain because of disease heterogeneity, phenotypic diversity, small patient populations, incomplete natural history and uncertainty of treatment effect in survival. The two new treatment options (inotersen and patisiran) appear to provide important benefits for patients, based on clinical trials short-term evidence. In this review, we discuss the disease natural survival course and currently available treatments impact on survival. We also discuss the importance of treatment choice (and or sequence of treatments) to maximize survival, while preserving the patient’s health-related quality of life.

DOI: 10.29245/2572.942X/2019/1.1242 View / Download Pdf View Full Text
Vol 4-1 Commentary

Commentary: Fc Gamma Receptors are Expressed in the Developing Rat Brain and Activate Downstream Signaling Molecules upon Cross-Linking with Immune Complex

Marianna Stamou1, Pamela J Lein2

11Department of Molecular Biosciences, School of Veterinary Medicine, 1089 Veterinary Medicine Drive, University of California, Davis, CA 95616

22ETH Zurich, Department of Health Sciences and Technology, Institute of Molecular Systems Biology, 8093 Zürich, Switzerland

DOI: 10.29245/2572.942X/2019/1.1243 View / Download Pdf View Full Text
Vol 4-1 Mini Review

Pheochromocytoma (PC 12) as a Model Cell Line for Membrane Permeabilization Studies in the presence of Electromagnetic Fields (EMFs): Recent Advances

Palalle G. Tharushi Perera1, Olha Bazaka2, Kateryna Bazaka3, Dominique Appadoo4, Rodney J. Croft5, Russell J. Crawford2, Elena P. Ivanova2*

1Faculty of Science, Engineering and Technology, Swinburne University of Technology, PO Box 218, Hawthorn, Vic 3122, Australia

2School of Science, RMIT University, PO Box 2476, Melbourne, Vic 3001, Australia

3Institute for Future Environments, Queensland University of Technology, GPO Box 2434. Brisbane, QLD 4001, Australia

4THz/Far-Infrared Beamline, Australian Synchrotron, Clayton, VIC 3168, Australia

5School of Psychology, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia

Pheochromocytoma PC 12 cell line is an established model system for neurosecretion and neuronal differentiation, particular to study cellular responses to nerve growth factors (NGF) and how these lead to expression of differentiation-specific proteins and differentiation. More recently, PC 12 has become a model system for investigating cell membrane permeabilization and cell attachment on different substrata. Of particular interest is the use of PC 12 to study the fundamental responses of cells to electromagnetic fields (EMFs) of 18 GHz and THz in the range of 0.3-19.5×1012 Hz, a type of radiation treatment shown to induce membrane depolarization and transient increase in permeability with no changes in cell viability, morphology, proliferation and cellular physiology. This makes EMFs of 18 GHz and THz radiation a promising alternative to conventional poration techniques for drug and gene delivery applications. This article will review recent progress in the use of PC 12 to investigate EMF radiation-induced cell membrane permeability, as well as to study mammalian cell attachment preferences and differentiation on polymer surfaces, including those coated with high molecular weight proteins of the extracellular matrix, e.g. laminins, poly-l-lysine, fibronectin, and on novel metallic surfaces of nanostructured titanium.

DOI: 10.29245/2572.942X/2019/1.1240 View / Download Pdf View Full Text