The Aggravating Role of Failing Neuropeptide Networks in the Development of Sporadic Alzheimer's Disease

Int J Mol Sci. 2024 Dec 5;25(23):13086. doi: 10.3390/ijms252313086.

Abstract

Alzheimer's disease imposes an increasing burden on aging Western societies. The disorder most frequently appears in its sporadic form, which can be caused by environmental and polygenic factors or monogenic conditions of incomplete penetrance. According to the authors, in the majority of cases, Alzheimer's disease represents an aggravated form of the natural aging of the central nervous system. It can be characterized by the decreased elimination of amyloid β1-42 and the concomitant accumulation of degradation-resistant amyloid plaques. In the present paper, the dysfunction of neuropeptide regulators, which contributes to the pathophysiologic acceleration of senile dementia, is reviewed. However, in the present review, exclusively those neuropeptides or neuropeptide families are scrutinized, and the authors' investigations into their physiologic and pathophysiologic activities have made significant contributions to the literature. Therefore, the pathophysiologic role of orexins, neuromedins, RFamides, corticotrope-releasing hormone family, growth hormone-releasing hormone, gonadotropin-releasing hormone, ghrelin, apelin, and natriuretic peptides are discussed in detail. Finally, the therapeutic potential of neuropeptide antagonists and agonists in the inhibition of disease progression is discussed here.

Keywords: Alzheimer’s disease; CRF; GHRH; GnRH; RFamides; apelin; ghrelin; neuromedin; neuropeptide; orexin; urocortin.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Humans
  • Neuropeptides* / metabolism

Substances

  • Neuropeptides
  • Amyloid beta-Peptides

Grants and funding

This research received no external funding.