Adrenomedullin, a Novel Target for Neurodegenerative Diseases

Abstract

Neurodegenerative diseases represent a heterogeneous group of disorders whose common characteristic is the progressive degeneration of neuronal structure and function. Although much knowledge has been accumulated on the pathophysiology of neurodegenerative diseases over the years, more efforts are needed to understand the processes that underlie these diseases and hence to propose new treatments. Adrenomedullin (AM) is a multifunctional peptide involved in vasodilation, hormone secretion, antimicrobial defense, cellular growth, and angiogenesis. In neurons, AM and related peptides are associated with some structural and functional cytoskeletal proteins that interfere with microtubule dynamics. Furthermore, AM may intervene in neuronal dysfunction through other mechanisms such as immune and inflammatory response, apoptosis, or calcium dyshomeostasis. Alterations in AM expression have been described in neurodegenerative processes such as Alzheimer's disease or vascular dementia. This review addresses the current state of knowledge on AM and its possible implication in neurodegenerative diseases.

Expression of the CGRP Family of Neuropeptides and their Receptors in the Trigeminal Ganglion

“…AM has been found to be generally expressed and to participate in a variety of physiological functions including vasodilation, bronchodilation, growth, and hormone regulation (Ferrero et al 2018b). Furthermore, AM is involved in several pathophysiological processes such as hypertension, retinopathy, and tumor genesis (Ferrero et al 2018a).…”

Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review

“…The incidence of AD increases exponentially after the age of 65 and nearly doubles every five years from 65 to 90 years of age . According to the literature one in four people aged 85 and over may present AD symptoms . In addition to aging, there are other potential risk factors associated with AD such as hypertension, metabolic disorders, obesity at midlife, diabetes, depression, physical inactivity, and low levels of education …”

“…that performs an important role or is related to some signaling pathway affecting the disorder. In addition to these biological targets mentioned above, many others have also been related to AD pathophysiological hypotheses and all have been used in AD drug discovery studies, including those involving in silico methods, also known as computer‐aided drug design (CADD) …”

“…[4] According to the literature [7] one in four people aged 85 and over may present AD symptoms. [8] In addition to aging, there are other potential risk factorsa ssociated with AD such as hypertension,m etabolic disorders, obesity at midlife, diabetes, depression,physical inactivity,and low levels of education. [4,6] AD is as evere social ande conomic health burden to moderns ociety,e specially considering the estimated total worldwide cost of about one trillion US dollarsi n2 018.…”

“…that performs an importantr ole or is related to some signaling pathway affecting the disorder.I na ddition to theseb iological targets mentioned above, many othersh ave also been relatedt oA Dp athophysiological hypotheses and all have been used in AD drug discovery studies, including those involving in silico methods, also known as computer-aided drugdesign (CADD). [1,8,23,24] The CADD of new potentiall igands that show biological activity or affinity toward AD targets is very promising,a sr eviewedr ecently. [25][26][27][28] Nevertheless, few of these reports are focused on the mechanism of action,n or do they consider the possibility of alternative mechanisms that occur betweent hese ligandsa nd the corresponding targets.…”