Estrogen and neurodegenerative diseases

Source: Wikipedia, the free encyclopedia.
Estradiol, the major estrogen sex hormone in humans

postmenopausal women. Estrogen and estrogen-like molecules form a large family of potentially beneficial alternatives that can have dramatic effects on human homeostasis and disease. Subsequently, large-scale efforts were initiated to screen for useful estrogen family molecules. Furthermore, scientists discovered new ways to synthesize estrogen-like compounds that can avoid many side effects.[citation needed
]

Estrogen

17-alpha- vs 17-beta-estradiol
Main article: Estrogen

Estrogen is a lipid

cognitive disorders, and can affect many important genes related to normal physiological function.[citation needed
]

Estrogen can be divided into four classes: 1) Animal Estrogens that includes

xenoestrogens). Xenoestrogens contain a large number of compounds that are synthesized or naturally exist. These estrogens imitate estrogen structure and can be designed to satisfy the need of new drugs. They may have a significant impact on neurodegenerative disease treatment due to their ease of synthesis and targeted specificity.[citation needed
]

Application

The application of estrogen on medicine can be divided into a number of aspects. The best known ones are

coronary heart disease. Estrogen also plays very important role in animal metabolism balance. These unexpected diseases hindered estrogen to get involved in neurodegenerative disease therapy. So, when applying estrogen-like drugs to relieve neurodegenerative diseases, the concentration should be restrictly controlled to avoid these side effects.[citation needed
]

Neurodegenerative Diseases

Parasagittal MRI of human head in patient with benign familial macrocephaly prior to brain injury (ANIMATED)
Main article:
Neurodegeneration

Neurodegenerative diseases are diseases caused along the process of

protein misfolding, intracellular mechanisms and programmed cell death
. Main classes of neurodegenerative diseases are
Amyotrophic lateral sclerosis.[citation needed
]

Efforts Made on Therapy

Different neurodegenerative diseases have different causes and are not well studied until now. There is no clear cure for such diseases but some efforts have been made to research deeper into them. The 10th Global College of Neuroproetction and Neuroregeneration Annual Conference together with the International Association of Neurorestoratology VI was held to discuss on neurorestoration, neuroprotection and neuroregeneration in various clinical neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's disease, stroke and brain or spinal cord injuries.[4] The main aim was to enhance health care by the use of stem cells, nanodrug delivery of drugs and stem cells, use of multimodal drugs as well as a combination of different approaches. They concluded that the future of neuroprotection could be achieved by the use of stem cells and nanodrug delivery in chronic neurological disorders.[4]

Estrogen and neurodegenerative diseases

Although estrogen is best known for its effects on the maturation and differentiation of the primary and secondary sex organs, increasing evidence suggests that its influence extends beyond this system, and its activity in the

cognitive decline seen in aged and disease-affected individuals.[5]
There is sufficient evidence that estradiol is a powerful
neuroprotectant which might have use against AD, stroke and Parkinson's disease both in women and men.[5]

Estrogen and Alzheimer's disease

This figure shows how APP cleavage produces toxic Abeta in Alzheimer's disease.

Amyloid precursor protein (APP) proteolysis is fundamental for production of Aβ peptides implicated in AD pathology.[6] By using a cell line that contains high levels of estrogen receptors, scientists found that treatment with physiological concentrations of 17 beta-estradiol is associated with accumulation in the conditioned medium of an amino-terminal cleavage product of APP (soluble APP or protease nexin-2), indicative of non-amyloidogenic processing.[7]

Estrogen and Parkinson's disease

Recommendations on the use of postmenopausal

L-dopa.[9]

Estrogen and Huntington's disease

Huntington's disease (HD) is a polyglutamine disorder based on an expanded CAG triplet repeat[10] leading to cerebral and striatal neurodegeneration.[11] Potential sex differences concerning the age of onset and the course of the disease are poorly defined, as the difficulties of matching female and male HD patients regarding their CAG repeat lengths limit comparability.[12]

Estrogen and Amyotrophic lateral sclerosis

ALS occurs more commonly in men than in women, and women get the disease later in life compared to men.[13] This suggested the possible protective role of estrogen in ALS. By conducting treatment of 17β-estradiol to

ovariectomy treated mice, scientists found significantly delay of disease progression.[14]

Estrogen Replacement Therapy

Main article:
Hormone Replacement Therapy

Estrogen Replacement Therapy (HRT) is a kind of hormone replacement therapy
. Its goal is to mitigate discomfort caused by diminished circulating estrogen after menopause. The 2002
The Million Women Study. As a result of these findings, the number of women taking hormone treatment dropped precipitously.[16] The Women's Health Initiative recommended that women with non-surgical menopause take the lowest feasible dose of HRT for the shortest possible time to minimize associated risks.[15]

Main Pathways

The role of estrogens is mostly mediated by two nuclear receptors (ER alpha and ER beta) and a membrane-associated G-protein (GPR30 or GPER), and it is not limited to reproduction, but it extends to the skeletal, cardiovascular and central nervous systems. Various pathologies such as cancer, inflammatory, neurodegenerative and metabolic diseases are often associated with dysfunctions of the estrogen system. Therapeutic interventions by agents that affect the estrogen signaling pathway might be useful in the treatment of many dissimilar diseases.[17] These pathways also shown great impact on neurodegenerative disease.[citation needed]

Application

The receptors of estrogen are specially distributed in different tissues, which have different influence on their downstream genes. The activation of the two different estrogen receptors has different effects on human. ERα and ERβ also mediate

Selective estrogen-receptor modulators' (SERMs') function,[18] but the selective ERα agitator can always cause some side effects such as breast cancer or endometrial hyperplasia, while the selective ERβ agitator may play an active effect on such diseases. So, the selective ERβ agitator has more clinical value for neurodegenerative diseases). In post-menopausal women, high levels of testosterone and estrogen higher the risk 2-3 times than lower level situation. Women that are not taking hormone replacement therapy (HRT) have lesser risk of breast cancer because of the insulin level increase.[19]

Nonsteroidal estrogens and neurodegenerative diseases

Nonsteroidal estrogens include

mycoestrogens
. They are very useful in neurodegenerative diseases' therapy when considering about the side effects caused by estradiol. As the development of chemical synthesis, it becomes possible for people to construct new molecules. Drug companies can exploit naturally existing compounds and synthetic compounds that have estrogen-like activity to produce patented proprietary drugs, especially the
contraceptives.[20]
17beta-estradiol thus may cause estrogenic or anti-estrogenic effects.[21]

Application

Nonsteroidal estrogens prevalently exist in our environment and have both positive and negative effects on our daily life. But as a possible way to get access to neurodegenerative disease treatment, scientists have developed multiple ways to screen these estrogens and select the ones that have less side effects. Bipartite recombinant yeast system and dual fluorescence report system are designed to screen these potential chemicals.[22][23]

References

  1. S2CID 43648760
    .
  2. PMID 15466938
    .
  3. PMID 11181953
    .
  4. ^
    S2CID 24356630
    .
  5. ^
    S2CID 12116802
    .
  6. PMID 23977176
    .
  7. PMID 8175728
    .
  8. PMID 12700049
    .
  9. S2CID 24749803
    .
  10. S2CID 802885
    .
  11. PMID 9596408
    .
  12. PMID 18502785
    .
  13. S2CID 29442303
    .
  14. S2CID 38207502
    .
  15. ^
    PMID 12117397
    .
  16. PMID 19196674
    .
  17. S2CID 6259593
    .
  18. PMID 12584371
    .
  19. ^ Tariq, Rabia; Sadia Huma; Mariam Zaka Butt; Fatima Amin (August 2013). "Risk factors and prevalence of breast cancer- a review". Journal of Pakistan Medical Association. 63 (8): 1075–1078.
  20. ^ "Natural Estrogens".
  21. ^ Phytoestrogen
  22. S2CID 36754149
    .
  23. PMID 23726343
    .
Retrieved from "https://en.wikipedia.org/w/index.php?title=Estrogen_and_neurodegenerative_diseases&oldid=1190778993"