NHE
I sure hope you find that abstract about Avonex and brain atrophy. I thought I recalled reading something to the effect that a placebo group displayed less brain atrophy after two years on
interferons.
Bromley
I appreciate your posting follow-up information from the conference. I definitely think neuroprotection is the future of MS management. You’ve given me a perfect opportunity to post some information about hormones and neuroprotection.
The information is not specific to MS but I think it illustrates the future potential of hormones to help manage it.
Progesterone (Guys, you have progesterone too, just not quite as much as women.)
Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination
Quote:
….locally synthesized PROG are likely to play an important role in the viability of neurons and in the formation of myelin sheaths.
Local synthesis of PROG in the brain and the neuroprotective and promyelinating effects of this neurosteroid offer interesting therapeutic possibilities for the prevention and treatment of neurodegenerative diseases, for accelerating regenerative processes and for preserving cognitive functions during aging.
Progesterone up-regulates neuronal brain-derived neurotrophic factor expression in the injured spinal cordQuote:
Our findings suggest that PROG enhancement of endogenous neuronal BDNF could provide a trophic environment within the lesioned spinal cord and might be part of the PROG activated-pathways to provide neuroprotection.
EstrogensThe antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic propertiesQuote:
Among the family of steroidal molecules, only estrogens have the capability of preventing neuronal cell death caused by increased oxidative burden.
Neuroprotection by estradiolQuote:
Thus, our view of the role of estrogen in neural function must be broadened to include not only its function in neuroendocrine regulation and reproductive behaviors, but also to include a direct protective role in response to degenerative disease or injury. Estrogen may play this protective role through several routes. Key among these are estrogen dependent alterations in cell survival, axonal sprouting, regenerative responses, enhanced synaptic transmission and enhanced neurogenesis.
Minireview: neuroprotective effects of estrogen-new insights into mechanisms of actionQuote:
An accumulating body of evidence clearly establishes that estradiol is a potent neuroprotective and neurotrophic factor in the adult
The role of the estrogen in neuroprotection: implications for neurodegenerative diseasesQuote:
Although data from human studies remains highly controversial, a large body of research findings suggests that this hormone plays a pivotal role in retarding and preventing the formation of neurodegenerative diseases through its receptor.
Estrogen receptor-mediated neuroprotection from oxidative stress requires activation of the mitogen-actived protein kinase pathwayQuote:
This study demonstrates that activation of either ERalpha or ERbeta can result in neuroprotection and that activation of the MAPK pathway is an important part of the neuroprotective mechanism.
Estrogen receptor subtypes alpha and beta contribute to neuroprotection and increased Bcl-2 expression in primary hippocampal neuronsQuote:
Using three indicators of neuronal viability and survival, we demonstrated that both the ERalpha selective agonist PPT and the ERbeta selective agonist DPN protected hippocampal neurons against glutamate-induced cell death in a dose-dependent manner,
As ERbeta is highly expressed in the brain and has little or no expression in the breast or uterus, discovery and design of ERbeta selective molecules could provide a strategy for activating the beneficial effects of estrogen in the brain without activating untoward effects of estrogen in reproductive organs.
Guys, I think there is some work already underway to
design selective estrogen receptor modulators (SERMS) for MS to eliminate “feminizing” effects of estrogens.
We’re all doing our best to see that bright spot at the end of the tunnel. Take care everyone. I’m marinating my brain in hormones and pharmaceuticals.
Sharon
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