McMaster University

Medical Sciences
Graduate Program

Scope of Search


Margaret Fahnestock

Margaret Fahnestock



Research Interests

Neurotrophic factors are proteins essential for nervous system development and function. The biosynthesis and regulation of neurotrophins such as NGF and BDNF are disrupted in many neurodegenerative and psychiatric diseases. My laboratory studies neurotrophin gene expression, regulation, signaling and trafficking and their role in Alzheimer's disease and autism. By studying dysregulation of NGF and BDNF in these disorders, we have come to understand how the proper amount of neurotrophin reaches the proper cells at the right time, and the consequences if it doesn’t. We use human post mortem brain tissue, animal models and cell culture to study transcriptional, translational and post-translational regulation, signaling and transport of neurotrophins and their receptors in health and disease. Understanding how neurotrophins are dysregulated in Alzheimer’s disease and autism is crucial to identifying new therapeutic approaches and targets for these devastating disorders.



Current projects include:

  1. Molecular mechanisms of BDNF transcriptional down-regulation and proNGF protein dysfunction in Alzheimer’s disease
  2. BDNF post-translational modification and signaling pathway disruptions in autism
  3. Axonal transport of pro-neurotrophins
  4. Mechanisms of lifestyle influences on neurotrophin levels



Molecular biology, biochemistry, cell culture, real-time qRT-PCR, Western blotting, ELISA, neurite outgrowth assays, animal models, behavioural assays.


McMaster University
Health Sciences Centre

telephone: (905) 525-9140 ext. 23344


Program Area

Physiology & Pharmacology


Research Areas

Molecular Neurobiology

Selected Publications

1. Retrograde axonal transport of BDNF and proNGF diminishes with age in basal forebrain cholinergic neurons.
Shekari A, Fahnestock M. Neurobiol Aging. 2019 Dec;84:131-140.
2. The Effects of Physical Exercise and Cognitive Training on Memory and Neurotrophic Factors.
Heisz JJ, Clark IB, Bonin K, Paolucci EM, Michalski B, Becker S, Fahnestock M. J Cogn Neurosci. 2017 Nov;29(11):1895-1907.
3. ProNGF, but Not NGF, Switches from Neurotrophic to Apoptotic Activity in Response to Reductions in TrkA Receptor Levels.
Ioannou MS, Fahnestock M. Int J Mol Sci. 2017 Mar 9;18(3). pii: E599.
4. Tau downregulates BDNF expression in animal and cellular models of Alzheimer's disease.
Rosa E, Mahendram S, Ke YD, Ittner LM, Ginsberg SD, Fahnestock M. Neurobiol Aging. 2016 Dec;48:135-142.
5. Decreased mTOR signaling pathway in human idiopathic autism and in rats exposed to valproic acid.
Nicolini C, Ahn Y, Michalski B, Rho JM, Fahnestock M. Acta Neuropathol Commun. 2015 Jan 20;3:3.