Vol 2-9 Mini Review

DCP-LA, a New Strategy for Alzheimer's Disease Therapy

Tomoyuki Nishizaki*

Innovative Bioinformation Research Organization, 2-3-14 Katsuragi, Kita-ku, Kobe 651-1223, Japan

Alzheimer’s disease (AD) is characterized by extensive deposition of amyloid β (Aβ) and formation of neurofibrillary tangles (NFTs) consisting of hyperphosphorylated Tau. So far, a variety of AD drugs targeting Aβ have been developed, but ended in failure. A recent focus on AD therapy, therefore, is development of Tau-targeted drugs. Aβ activates glycogen synthase kinase-3β (GSK-3β), that plays a central role in Tau phosphorylation, responsible for NFT formation. The linoleic acid derivative DCP-LA has been developed as a promising drug for AD therapy. DCP-LA serves as a selective activator of PKCε and a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B). DCP-LA restrains Tau phosphorylation efficiently due to PKCε-mediated direct inactivation of GSK-3β, to PKCε/Akt-mediated inactivation of GSK-3β, and to receptor tyrosine kinase/insulin receptor substrate 1/phosphoinositide 3-kinase/3-phosphoinositide-dependent protein kinase 1/Akt-mediated inactivation of GSK-3β in association with PTP1B inhibition. Moreover, DCP-LA ameliorates spatial learning and memory impairment in 5xFAD transgenic mice, an animal model of AD. Consequently, combination of PKCβ activation and PTP1B inhibition must be an innovative strategy for AD therapy.

DOI: 10.29245/2572.942X/2017/9.1159 View / Download Pdf
Vol 2-9 Commentary

Commentary: Protective Effects of Isorhamnetin on N2a Cell Against Endoplasmic Reticulum Stress-induced Injury Is Mediated by PKC?

Lingyu Qiu, Huiqiang Lu*

Jiangxi Province Key Laboratory of Developmental Biology of Organs, Jiangxi Engineering laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Center for Developmental biology of Jinggangshan University, College of life sciences, Jinggangshan University, Ji’an, Jiangxi 343009, China

Neuronal apoptosis is an important pathophysiological factor of Alzheimer’s disease (AD). Inhibition of endoplasmic reticulum stress (ERS)-induced neuronal apoptosis is an effective strategy to deal with AD. In this commentary, we summarize the relationship between AD and ERS injury-induced neuronal apoptosis, and highlight the protective effects and mechanism of isorhamnetin (Iso) against ERS-induced injury in N2a cells. Moreover, this commentary discusses the recent findings in the role of Iso in other diseases.

DOI: 10.29245/2572.942X/2017/9.1160 View / Download Pdf
Vol 2-9 Commentary

Commentary: Heat stress-induced neuroinflammation and aberration in monoamine levels in hypothalamus are associated with temperature dysregulation

Nishant Ranjan Chauhan1, Rajinder Kumar Gupta1, Shashi Bala Singh2*

1Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organisation (DRDO), Lucknow Road, Timarpur, Delhi 110054, India
2Distinguished Scientist and Director General (Life Sciences), Defence Research and Development Organisation (DRDO), DRDO Bhawan, Rajaji Marg, Delhi 110011, India

Heat stress (HS) is a common stressor that affects all biological systems. Mild to moderate HS is associated with intact baroreflex response which tries to cope up with the stress by maintaining mean arterial pressure (MAP). However, during severe HS, baroreflex response fails leading to fall in MAP which is a pathognomonic feature of heat stroke. Heat stroke can induce neuroinflammation, brain ischemia, oxidative stress and neuronal damage. Increase in ambient temperature led to activation of the thermoregulatory process in Hypothalamus (HTH) and was achieved by rise in nor-epinephrine and fall in serotonin, whereas neurotransmitter imbalance occurred during severe HS in HTH and was associated with expression of inflammatory mediators. Results of our preliminary study also suggested that neuroinflammation was associated with neurotransmitter (monoamines and glutamate) imbalance in HTH leading to thermoregulatory disruption during severe HS. Here, we also discussed that individuals predisposed to factors like chronic inflammation and other complications could decrease the threshold of heat tolerance since a short episode of even sub maximal heat exposure would precipitate the inflammatory cascade leading to thermoregulatory shutdown.

DOI: 10.29245/2572.942X/2017/9.1150 View / Download Pdf
Vol 2-9 Mini Review

Neural Control and Precision of Spike Phasing in Flight Muscles

Fritz-Olaf Lehmann, PhD

Department of Animal Physiology, University of Rostock, Germany

Rhythmic locomotor behavior in animals requires exact timing of muscle activation within the locomotor cycle. Neural strategies for timing control that employ higher brain function, however, suffer from synaptic and neural transmission delays, making them inefficient for control of fast-frequent locomotor systems. Evolutionary pressure on muscle timing control is particularly pronounced in flying insects with wing flapping periods of few milliseconds. In these animals, sensory integration is often achieved at the level of the peripheral nervous system, circumventing the central brain and controlling spike activation phases with little delay, rather than muscle spike frequency. This review is engaged in the precision with which flies adjust power output of their flight muscles and highlights the significance of visual and proprioceptive feedback loops for muscle spike control. Recent results suggest that in flies peripheral feedback loops are keys enabling precise heading control and body stability in flight, and potentially similar to the function of local circuits for locomotor control found in the spinal chord of vertebrates.

DOI: 10.29245/2572.942X/2017/9.1153 View / Download Pdf
Vol 2-9 Commentary

Commentary: Identification of potential therapeutic compounds for Parkinson's disease using Drosophila and human cell models

Francisco José Sanz1,2, Cristina Solana-Manrique1,2, Verónica Muñoz-Soriano1,2 and Nuria Paricio1,2,*

1Departamento de Genética, Facultad CC Biológicas, Universidad de Valencia, 46100 Burjassot, Spain
2Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina (ERI BIOTECMED), Universidad de Valencia, 46100 Burjassot, Spain

DOI: 10.29245/2572.942X/2017/9.1149 View / Download Pdf