Gender differences in frontotemporal lobar degeneration (FTLD) have been reported in the literature but not well characterized or explored. In the present work, we propose that steroid hormone estrogens delay the onset of FTLD in pre-menopausal women compared to age equivalent men, and may provide neuroprotection in the early post-menopausal period. We present a model wherein estrogens serve a regulatory role in attenuating the microglia conversion from the benign to active form in response to cell stress that might otherwise trigger an inflammatory response. Via microglia stabilization, estrogens preserve the homeostasis of both the ubiquitin-proteosome degradation system and lysosome-autophagy recycling system. Both systems have been implicated in the genetic forms of FTLD, with the latter system recognized to be associated with the majority of them.
Part of the book: Sex Hormones in Neurodegenerative Processes and Diseases