Dr. Nirinjini Naidoo's research focus is on the interactions between sleep-wake behavior, aging and the ER stress response* (see figure for description). While sleep is a highly conserved behavior, very little is known about the homeostatic processes that underlie the function of sleep or what mediates sleep propensity. My general hypothesis is that the activity of the molecular components that underlie the ER stress response predicts sleep propensity and regulate aging. We have established that the endoplasmic reticulum is a critical sensor of perturbations that result from sleep deprivation and that a cellular protective pathway, the unfolded protein response (UPR)/ER stress response, is induced when mice or Drosophila are sleep deprived giving rise to the idea that the ER stress response may serve as a sensitive indicator of sleep dyshomeostasis. Recently completed studies indicate that this adaptive protective response is impaired in aged mice experiencing sleep loss. This suggests that inadequate sleep in the elderly, who normally experience sleep disturbances, leads to an impaired protective ER stress response that may in turn lead to further sleep disturbances beginning a vicious cycle of sleep loss and cellular damage.
Other research interests include studying the role of the synaptic scaffolding protein, Homer, in sleep-wake behavior and using proteomic approaches to understand some of the molecular mechanisms involved in sleep regulation and aging.
*The ER stress response is an adaptive signaling pathway that restores ER homeostasis when misfolded proteins accumulate in the ER. This is achieved by attenuating protein translation, up-regulating chaperones and increasing degradation of misfolded proteins. Unresolved accumulation of misfolded proteins leads to protein aggregates and proteotoxicity which is the basis of many neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
Naidoo N. Potential of proteomics as a bioanalytic technique for quantifying sleepiness. J Clin Sleep Med. 2011 Oct 15;7(5 Suppl):S28-30.
Naidoo N. The unfolded protein response in mouse cerebral cortex. Methods Enzymol. 2011;489:3-21.
Naidoo N, Zhu J, Zhu Y, Fenik P, Lian J, Galante R, Veasey S. Endoplasmic reticulum stress in wake-active neurons progresses with aging. Aging Cell. 2011 Aug;10(4):640-9.
McShane BB, Galante RJ, Jensen ST, Naidoo N, Pack AI, Wyner A. Characterization of the bout durations of sleep and wakefulness. J Neurosci Methods. 2010 Nov 30;193(2):321-33.
Nikonova EV, Naidoo N, Zhang L, Romer M, Cater JR, Scharf MT, Galante RJ, Pack AI. Changes in components of energy regulation in mouse cortex with increases in wakefulness. Sleep. 2010 Jul;33(7):889-900.
Naidoo N. Cellular Stress/The Unfolded Protein Response: Relevance to Sleep and Sleep Disorders, Sleep Medicine Reviews, Sleep Med Rev. 2009 Jun;13(3):195-204.
Naidoo N. ER and Aging - Protein Folding and the ER Stress Response, Ageing Research Reviews, epub April 2009.
Naidoo N, Ferber M, Master M, Zhu Y, Pack AI. Aging impairs the unfolded protein response to sleep deprivation and leads to proapoptotic signaling. J Neurosci. 2008 28: 6539-6548.
Pawlyck AC, Ferber M, Shah A, Pack AI, Naidoo N. Proteomic analysis of the effects and interactions of sleep deprivation and aging in mouse cerebral cortex. J Neurochem. 2007 Dec;103(6):2301-13.
Student Rotation Projects
1. Mechanism by which sleep loss leads to the ER stress response/UPR.
2. Genetic manipulation of components of the UPR pathway and subsequent effect on sleep.
3. Consequences of aging on both the ER stress response and sleep.
4. Proteomics of the aging endoplasmic reticulum.
5. The role of homer in sleep homeostasis.
University of Durban-Westville, South Africa MSc (Biochemistry) 1986
University of Pennsylvania, PhD (Chemistry) 1994