Deciphering the enigmatic crosstalk between prostate cancer and Alzheimer's disease: A current update on molecular mechanisms and combination therapy

Biochim Biophys Acta Mol Basis Dis. 2022 Nov 1;1868(11):166524. doi: 10.1016/j.bbadis.2022.166524. Epub 2022 Aug 17.

Abstract

Alzheimer's disease (AD) and prostate cancer (PCa) are considered the leading causes of death in elderly people worldwide. Although both these diseases have striking differences in their pathologies, a few underlying mechanisms are similar when cell survival is considered. In the current study, we employed an in-silico approach to decipher the possible role of bacterial proteins in the initiation and progression of AD and PCa. We further analyzed the molecular connections between these two life-threatening diseases. The androgen deprivation therapy used against PCa has been shown to promote castrate resistant PCa as well as AD. In addition, cell signaling pathways, such as Akt, IGF, and Wnt contribute to the progression of both AD and PCa. Besides, various proteins and genes are also common in disease progression. One such similarity is mTOR signaling. mTOR is the common downstream target for many signaling pathways and plays a vital role in both PCa and AD. Targeting mTOR can be a favorable line of treatment for both AD and PCa. However, drug resistance is one of the challenges in effective drug therapy. A few drugs that target mTOR have now become ineffective due to the development of resistance. In that regard, phytochemicals can be a rich source of novel drug candidates as they can act via multiple mechanisms. This review also presents mTOR targeting phytochemicals with promising anti-PCa, anti-AD activities, and approaches to overcome the issues associated with phytochemical-based therapies in clinical trials.

Keywords: Alzheimer's disease; In-silico; Nano-drug delivery; Phytochemicals; Prostate cancer; mTOR.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / genetics
  • Androgen Antagonists / therapeutic use
  • Androgens / metabolism
  • Bacterial Proteins
  • Humans
  • Male
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Androgen Antagonists
  • Androgens
  • Bacterial Proteins
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases