Development of genetic and pharmacological approaches for enhancing neuroprotection and nerve regeneration
Neurodegeneration and nerve damage are common medical problems of the nervous system. Standard medical and surgical practices are insufficient to cure or to slow progression of these diseases. Gene therapy is emerging as a powerful approach with potential to treat some of the diseases of the nervous system. We focus on Multiple system atrophy (MSA) as a neurodegenerative disease and on sciatica as an example of nerve damage. We propose new therapeutic strategies based on combining genes that are involved in these disorders. First, the potency of combining four genes was examined: brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) on the recovery of motor neuron function after crush injury of the sciatic nerve. Moreover, we evaluated the effect of combining three genes involved in glutamate metabolism and oxidative stress: excitatory amino acid transporter 2 (EAAT2), glutamate dehydrogenase (GDH2), and nuclear related factor 2 (Nrf2) in mouse models of MSA.
AD/PD, 2015, Nice.
ISFN, 2013,2014, Eilat
Monje F, Cicvaric A, Acevedo Aguilar J, Elbau I, Horvath O, Diao W, Glat M and Pollak D. Disrupted Ultradian Activity Rhythms and Differential Expression of Several Clock Genes in Interleukin-6-Deficient Mice. Front. Neurol 2017 March 22; 8:99.
Salomon-Zimri S, Glat M, Barh um Y, Ben-Zur T, Luz I, Bohem-Cagan A, Liraz O, Offen D, Michaelson D. Reversal of ApoE4-driven brain pathology by VEGF treatment. J of Alzheimer’s Disease. 2016 Jun 30;53(4):1443-58.
Glat M, Ben-Zur T, Barhum Y, Offen D. Neuroprotective Effect of a DJ-1 Based Peptide in a Toxin Induced Mouse Model of Multiple System Atrophy. PLoS One 2016 Feb 22;11 (2).
Glat M, Beninger F, Barhum Y, Ben-Zur T, Kogan E, Steiner I, Yaffe D, Offen D. Ectopic Muscle Expression of Neurotrophic Factors Improves Recovery After Nerve Injury. J. Mol Neurosci. 2016 Jan; 58(1):39-45.
Bennninger F, Glat M, Offen D, Steiner I. Glial fibrillary acidic protein as a marker of astrocytic activation in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis. J. Clin Neurosci. 2016 Apr; 26:75-8.
Glat M, Offen D. Cell and gene therapy in Alzheimer’s disease. Stem Cells Dev. 2013 May 15;22(10):1490-6. v
Glat M, Skaat H, Menkes-Caspi N, Margel S, Stern E. Age-dependent effects of microglial inhibition in vivo on Alzheimer's disease neuropathology using bioactive-conjugated iron oxide nanoparticles. J. Nanobiotechnology. 2013 Sep 23;11:32.
Research Categories: Cellular/molecular neuroscience