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Dr. Latha Diwakar, PhD
Senior Scientific Officer at the Centre for Brain Research
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Dr. Latha Diwakar obtained her masters in Bioscience from University of Mysore in the year 1996. She pursued her PhD on Gender related difference in pathogenesis of neurodegenerative disorders: role of mitochondrial dysfunction and protein thiol homeostasis at National Brain Research Centre, Manesar, India during 2005. Dr. Diwakar worked as Postdoctoral fellow from 2005-2008 in NIMHANS, Bengaluru, on animal model ischemia and Identification of genetic risk factors in young stroke patients with high homocysteine to understand etio-pathogenesis of stroke. From 2008 – 2015 she worked as independent Research scientist at Vittal Mallya Scientific Research Foundation, Bengaluru on evaluating many potential drug molecules for their molecular mechanisms of chronic inflammatory diseases funded by DST and DBT. She worked as Research faculty in TATA grant from 2015 at Centre for Neuroscience, Indian Institute of Science, on animal model of vascular dementia to know the commonality between vasoconstriction in brain and early AD in downstream pathways that drive to dementia.
Research
Dementia is a major public health issue in aging population with increasing life expectancy it becomes cause of concern in the society. It covers a spectrum of disorders including Alzheimer’s Disease (AD), Lewy body dementia and Vascular Dementia (VD) occurring as mixed dementia where vascular component plays an important role. Clinical studies have shown that cerebrovascular lesions seen as white matter hyperintensity in MRI of elderly population provides evidence for micro-infracts and micro-bleeds contribute to VD. We have developed an animal model of vascular dementia which can be utilized to study molecular underpinnings of disease pathogenesis simulating clinical scenario. Given such vascular insults in AD mice background could help us to understand the interplay between vasculature and Amyloid, which is important for deciphering the implication of vascular insult in patients ApoE risk allele. We have demonstrated for first time the commonality between vasoconstriction in brain and early AD in downstream pathways that drive the behavioral abnormalities. However single vascular insult in mice is reversible giving us opportunity to study the components involved in regeneration of vessels offering potential therapeutic avenues for people with vascular dysfunction.
People
Position
Publications
Verma A, Ray A, Bapat D, Diwakar L, Kommaddi RP, Schneider BL, Hirsch EC, and Ravindranath V. (2020), Glutaredoxin 1 Downregulation in the Substantia Nigra Leads to Dopaminergic Degeneration in Mice. Movement Disorders. doi:10.1002/(ISSN)1531-8257. 2020.
Ahmad F, Das D, Kommaddi RP, Diwakar L, Gowaikar R, Rupanagudi KV, Bennett DA, Ravindranath V. Isoform-specific hyperactivation of calpain-2 occurs presymptomatically at the synapse in Alzheimer's disease mice and correlates with memory deficits in human subjects. Sci Rep. 2018 Sep 3; 8(1):13119.
S Shenvi, KR Kiran, K Kumar, Diwakar L, GC Reddy. Synthesis and biological evaluation of boswellic acid-NSAID hybrid molecules as anti-inflammatory and anti-arthritic agents. European journal of medicinal chemistry 98, 170-178. 2015.
Samaga L, KK, Rao GV, Reddy GC, Kush AK, Diwakar L. Synthetic racemates of abyssinone I and II induces apoptosis through mitochondrial pathway in human cervix carcinoma cells. Bioorganic Chemistry 56: 54-61. 2014.
Shenvi S, Kumar K, Hatti KS, Rijesh K, Diwakar L, Reddy G.C. Synthesis, anticancer and antioxidant activities of 2,4,5-trimethoxy chalcones and analogues from asaronaldehyde: Sturcture-activity relationship. European Journal of Medicinal Chemistry 62 435-442. 2013.
Diwakar L, Rudresh Kumar KJ, Bachnalkar A, Ravindranath V, Christopher R, Nagaraja D. The influence of MTR A2756G polymorphism on plasma homocysteine in young south Indians. ClinChimActa. 395, 172-174. 2008.
Diwakar L, Ravindranath V. Inhibition of cystathionine-gamma-lyase leads to loss of glutathione and aggravation of mitochondrial dysfunction mediated by excitatory amino acid in the CNS. Neurochem Int. 50, 418-426. 2007.
Karunakaran S, Diwakar L, Saeed U, Agarwal V, Ramakrishnan S, Iyengar S, and Ravindranath V. Activation of apoptosis signal regulating kinase 1(ASK1) and translocation of death-associated protein, Daxx, in substantianigra pars compacta in a mouse model of Parkinson’s disease: protection by alpha-lipoic acid. FASEB J. 21:2226- 36. (Co- first author). 2007.
Diwakar L, Kenchappa RS, Annepu J, Saeed U, Sujanitha R, Ravindranath V, Down-regulation of glutaredoxin by estrogen receptor antagonist renders female mice susceptible to excitatory amino acid mediated complex I inhibition in CNS. Brain Res.1125(1):176-184. 2006.
Diwakar L, Kenchappa RS, Annepu J, Saeed U, Sujanitha R, Ravindranath V, Down-regulation of glutaredoxin by estrogen receptor antagonist renders female mice susceptible to excitatory amino acid mediated complex I inhibition in CNS. Brain Res.1125(1):176-184. 2006.
Kenchappa RS, Diwakar L, Annepu J, Ravindranath V. Estrogen and neuroprotection: higher constitutive expression of glutaredoxin in female mice offers protection against MPTP-mediated neurodegeneration. FASEB J. 18:1102-1114. (Co-first author). 2004.
Devi L, Diwakar L, Raju TR, Kutty BM. Selective neurodegeneration of hippocampus and entorhinal cortex correlates with spatial learning impairments in rats with bilateral ibotenate lesions of ventral subiculum. Brain Res. 960:9-15. 2003.
Kenchappa RS, Diwakar L, Boyd MR, Ravindranath V. Thioltransferase (glutaredoxin) mediates recovery of motor neurons from excitotoxic mitochondrial injury. J Neurosci. 22:8402-8410. 2002.
Contact
Centre for Brain Research
SID (Innovation centre) complex
Indian Institute of Science (IISc)
Malleswaram 18th Cross
Bangalore-560012
Karnataka, INDIA.
Email: latha[at]iisc.ac.in
Telephone: Office +91 80 2293 3588
