Acta Scientific Neurology (ASNE) (ISSN: 2582-1121)

Short Communication Volume 3 Issue 11

Does Estrogen Therapy Prevent Late Onset Alzheimer's Disease?

Thekkuttuparambil Ananthanarayanan Ajith*

Department of Biochemistry, Amala Institute of Medical Sciences, Amala Nagar, Kerala, India

*Corresponding Author: Thekkuttuparambil Ananthanarayanan Ajith, Professor of Biochemistry, Department of Biochemistry, Amala Institute of Medical Sciences, Amala Nagar, Kerala, India.

Received: September 29, 2020; Published: October 28, 2020

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  Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease remain a major challenge to human. Among the neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson’s disease are two major forms. According to the recent survey in US, more than 5.5 million (age 65 or older) people have dementia caused by Alzheimer’s and remain the 5th leading cause of death among the elders. World Health Organization (WHO) expected ~ 16.2% prevalence of AD among people over 65 years worldwide by 2050. The median survival of AD patients who diagnosed at age 65 years is estimated to be 9 years. The disease causes ~ 66-75% of household income for the management. Furthermore, due to behavioral disturbances, faecal and urinary incontinence and increase need for personal care of AD patients, prevalence of anxiety and depression were found among caregivers mainly female care givers. Despite large number of studies to find various mechanisms for AD, the exact molecular mechanism in the pathophysiology of this irreversible disease has not yet been established. Formation and deposition of extracellular β-amyloid peptide (Aβ, ~4 kDa protein) in an amyloidogenic pathway in the brain region leading to synaptic dysfunction, disrupting neural connectivity was demonstrated as well [1]. Aβ is formed from the β-amyloid precursor protein after processing by the membrane-bound multi-subunit aspartyl endoprotease, β- (exists in two forms BACE1 and BACE2) and γ-secretase. Presenilin1 or 2 (PS1 or PS2), subunit of γ – secretase was found to be mutated in familiar AD cases. In addition to this, several forms of mutations in the β-amyloid precursor protein were also evidenced. Among the different Aβ species found, the one ending at position 40 (Aβ40) are present in 80 - 90% cases, followed by slightly longer forms Aβ 42 in 5 - 10% cases. Aβ42 are more toxic due to its fibrillogenic and hydrophobic nature.

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References

  1. Murphy MP and Vine HL. “Alzheimer’s Disease and the β-Amyloid Peptide”. Journal of Alzheimer's Disease 19 (2010): 31.
  2. Farris W., et al. “Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain In vivo”. Proceedings of the National Academy of Sciences of the United States of America 100 (2003): 4162-4167.
  3. Qiu WQ and Folstein MF. “Insulin, insulin-degrading enzyme and amyloid-beta peptide in Alzheimer’s disease: review and hypothesis”. Neurobiology of Aging 27 (2006): 190-198.
  4. Caccamo A., et al. “Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders”. Neurobiology of Aging 26 (2005): 645-654.
  5. Ajith TA and Padmajanair G. “Mitochondrial pharmaceutics: A new therapeutic strategy to ameliorate oxidative stress in Alzheimer's disease”. Current Aging Science 8 (2015): 235-240.
  6. Stephenson J., et al. “Inflammation in CNS neurodegenerative diseases”. Immunology 154 (2018): 204-219.
  7. Eichenbaum H. “A cortical-Hippocampal system for declarative memory”. Nature Reviews Neuroscience 1 (2000): 41-50.
  8. Warren MP and Halpert S. “Hormone replacement therapy: controversies, pros and cons”. Best Practice and Research Clinical Endocrinology and Metabolism 18 (2004): 317-332.
  9. Prokai L., et al. “Quinol-based cyclic antioxidant mechanism in estrogen neuroprotection”. Proceedings of the National Academy of Sciences of the United States of America 100 (2003): 11741-11746.
  10. Petrovic S., et al. “Estradiol affects calcium transport across mitochondrial membrane in different brain regions”. Annals of the New York Academy of Sciences 1048 (2005): 341-343.
  11. Sribnick EA., et al. “17beta-estradiol attenuates glutamate-induced apoptosis and preserves electrophysiologic function in primary cortical neurons”. Journal of Neuroscience Research 76 (2004): 688-696.
  12. Zhao L., et al. “17beta-Estradiol regulates insulin-degrading enzyme expression via an ERbeta/PI3-K pathway in hippocampus: relevance to Alzheimer's prevention”. Neurobiology of Aging 32 (2011): 1949-1963.
  13. Viña J and Lloret A. “Why women have more Alzheimer's disease than men: gender and mitochondrial toxicity of amyloid-beta peptide”. Journal of Alzheimer's Disease 20 (2010): S527-S533.
  14. Wang L., et al. “Estrogen receptor (ER)beta knockout mice reveal a role for ERbeta in migration of cortical neurons in the developing brain”. Proceedings of the National Academy of Sciences of the United States of America 100 (2003): 703-708.
  15. Zhao L., et al. “17β-Estradiol regulates insulin-degrading enzyme expression via an ERβ/PI3-K pathway in hippocampus: relevance to Alzheimer’s prevention”. Neurobiology of Aging 32 (2011): 1949-1963.
  16. “Alzheimer's Disease and Aging: Therapeutic Potential of Estrogen”. Clinical Trials Identifier
  17. Henderson V., et al. “Prior use of hormone therapy and incident Alzheimer’s disease in the Women’s Health Initiative Memory Study”. The American Academy of Neurology S31 (2007): 4.
  18. Imtiaz B., et al. “Risk of Alzheimer's disease among users of postmenopausal hormone therapy: A nationwide case-control study”. Maturitas 98 (2017): 7-13.
  19. Mikkola TS., et al. “Lower Death Risk for Vascular Dementia Than for Alzheimer's Disease With Postmenopausal Hormone Therapy Users”. Metab 102 (2017): 870-877.
  20. Savolainen-Peltonen H., et al. “Use of postmenopausal hormone therapy and risk of Alzheimer's disease in Finland: nationwide case-control study”. British Medical Journal 364 (2019): l665.
  21. Schierbeck LL., et al. “Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial”. British Medical Journal 345 (2012): e6409.
  22. Gialeraki A., et al. “Oral Contraceptives and HRT Risk of Thrombosis”. Clinical and Applied Thrombosis/Hemostasis 24 (2018): 217-225.
  23. Bhavnani BR., et al. “Pharmacology of Conjugated Equine Estrogens: Efficacy, Safety and Mechanism of Action”. The Journal of Steroid Biochemistry and Molecular Biology 142 (2014): 16-29.
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Citation

Citation: Thekkuttuparambil Ananthanarayanan Ajith. “Does Estrogen Therapy Prevent Late Onset Alzheimer's Disease?". Acta Scientific Neurology 3.11 (2020): 105-107.



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