Constanza J Cortes
Assistant Professor - Tack V in Neurology

I work on understanding the potential role of muscle protein quality control on brain aging. This work is completely novel, suggesting that our brains do not exist (and age) in isolation, but rather as an integrated part of a physiological system. My research represents a cutting edge approach to our understanding of brain plasticity and aging, as it suggests that distant tissues such as skeletal muscle may be fundamentally influencing the rate at which our brain ages.

Current Research Interests

Protein homeostasis (also known as ‘proteostasis’), is fundamental for the survival of neurons, and proteostasis dysfunction is a feature of many neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. Understanding the mechanisms underlying proteostasis dysfunction, and uncovering novel targets for rescuing these defects may yield important therapeutic targets for diseases associated with proteostasis failure.

I have uncovered a previously unreported periphery-to-CNS signaling network originating in skeletal muscle. Using a conditional skeletal-muscle specific transgenic mouse model for a master regulator of cellular clearance and metabolism, I have shown improved proteostasis in the CNS during normal aging. This suggest that maintaining skeletal muscle proteostasis during aging may yield important neuroprotective benefits in the aging brain. In agreement with this, these muscle-specific proteostasis-activated mice perform significantly better in neurocognitive testing at 18 months of age compared to their age-matched control littermates. This suggests the existence of secreted signals originating in skeletal muscle and targeting the CNS, resulting in improved proteostasis control in the brain. My current work focuses on identifying those signals, and testing their ability to rescue neurodegenerative ‘proteinopathies’, including Alzheimer’s disease.

Current Appointments & Affiliations

Contact Information

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