Our goal is to understand how hormones shape the female brain, and why women face a higher burden of neurodegenerative disease.
Women are disproportionately affected by Alzheimer's disease, and the menopause transition reshapes the brain's entire hormonal environment. Understanding why sits at the heart of women's brain health, and at the heart of what we do. The interaction between sex hormones and brain mitochondria is a complex area of study with profound implications for brain health and disease. Mitochondria, known as the powerhouse of the cell for their role in generating adenosine triphosphate (ATP), are involved in far more than energy production, including calcium buffering, reactive oxygen species (ROS) regulation, apoptosis, and critical signalling pathways for neuronal survival and synaptic plasticity. Traditionally associated with reproduction, androgens and estrogens also play essential roles in neuroprotection, cognition, learning, and mood regulation. Their levels fluctuate and decline across the lifespan, a key to understanding why neurodegenerative diseases such as Alzheimer's strike women more often.
Understanding how sex hormones regulate mitochondrial dynamics in both healthy and diseased brains is essential to uncovering the biological mechanisms that drive sex differences in brain ageing and vulnerability to neurodegeneration. By elucidating the interplay between hormones and mitochondria, our team aims to identify novel therapeutic targets to counteract mitochondrial dysfunction, a key contributor to age-related cognitive decline. Our work has revealed critical pathways through which hormonal signalling shapes brain resilience or susceptibility, guiding the development of sex-specific interventions to promote healthy brain ageing, and placing women's brain health, for too long understudied, at the centre of the conversation.
Fig. 1- Determinants of brain health and neurodegeneration. Multiple, interacting factors, genetics, epigenetics, ageing, gonadal and brain hormones, metabolism and diet, converge to shape core brain functions such as cognition, plasticity, neurogenesis and neuroprotection, and ultimately the risk of neurodegeneration. Within this landscape, our lab focuses on the role of sex hormones and their crosstalk with metabolism and ageing, to understand the mitochondrial mechanisms driving sex differences in brain vulnerability and to advance women's brain health.
