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Latha Diwakar's Lab

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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 from University of Mysore in the year 1996. She pursued her PhD on Gender related difference in pathogenesis of neurodegenerative disorders finding the 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 covering a spectrum of disorders including Alzheimer’s Disease (AD), Lewy body dementia and Vascular Dementia (VD). These are multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. 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. Therefore reducing the incidence of dementia and its impact on quality of life will require targeting interventions at very early stages of the disease process, before substantial neuronal damage occurs.

We have developed an animal model of vascular dementia which can be manipulated to explore molecular underpinnings of disease pathogenesis simulating clinical scenario. Given such vascular insults in AD mice background could help us to understand the interplay between early cerebrovascular dysfunction with progressive synaptic dysfunction and formation of classic AD the plaques as well as neurofibrillary tangles. Such studies are important for deciphering the implication of vascular insult in patients with AD risk allele. We have demonstrated for first time the commonality between vasoconstriction in brain and early AD dysfunction in downstream pathways that drive the pathogenesis. 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

Project assistant position available: Postgraduates with life science background interested in working on Vascular dementia and Alzheimer’s disease can contact latha@iisc.ac.in for on going projects.

Publications

Selected 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