Multiple beneficial effects of melanocortin MC4 receptor agonists in experimental neurodegenerative disorders: Therapeutic perspectives

Giuliani, Daniela; Ottani, Alessandra; Neri, Laura; Zaffe, Davide; Grieco, Paolo; Jochem, Jerzy; Cavallini, Gian Maria; Catania, Anna; Guarini, Salvatore

doi:10.1016/j.pneurobio.2016.11.004

Cited by 30 publications

(27 citation statements)

References 269 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Endogenous ACTH and other melanocortins, as well as presumably exogenously administered ACTH, can access the CNS in the brain stem and the hypothalamus, bind to MCR, particularly MC4R, and initiate signaling [ 10 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ]. These brain stem neurons trigger vagal activity with release of acetylcholine (ACh) in peripheral tissue, with binding and activation of acetylcholine receptors (AChR).…”

Section: Direct Effects In the Cnsmentioning

confidence: 99%

“…A recent study shows that constitutive activity of MC4R inhibits L-type voltage-gated calcium channels in cultured neurons [ 63 ]. Activation of MC4R shows neuroprotective and neuroregenerative effects in several models of neurodegenerative diseases [ 52 ], including neurogenesis and cognitive recovery in an animal model of Alzheimer’s disease [ 64 ]. We reported that the MCR agonist ACTH1-39 protects cultured rat forebrain neurons from excitotoxic, apoptotic, oxidative and inflammation related insults [ 65 ], but the specific MCR subtypes involved are not known.…”

Section: Direct Effects In the Cnsmentioning

confidence: 99%

See 1 more Smart Citation

Melanocortins, Melanocortin Receptors and Multiple Sclerosis

Lisak

Benjamins

2017

Brain Sciences

View full text Add to dashboard Cite

The melanocortins and their receptors have been extensively investigated for their roles in the hypothalamo-pituitary-adrenal axis, but to a lesser extent in immune cells and in the nervous system outside the hypothalamic axis. This review discusses corticosteroid dependent and independent effects of melanocortins on the peripheral immune system, central nervous system (CNS) effects mediated through neuronal regulation of immune system function, and direct effects on endogenous cells in the CNS. We have focused on the expression and function of melanocortin receptors in oligodendroglia (OL), the myelin producing cells of the CNS, with the goal of identifying new therapeutic approaches to decrease CNS damage in multiple sclerosis as well as to promote repair. It is clear that melanocortin signaling through their receptors in the CNS has potential for neuroprotection and repair in diseases like MS. Effects of melanocortins on the immune system by direct effects on the circulating cells (lymphocytes and monocytes) and by signaling through CNS cells in regions lacking a mature blood brain barrier are clear. However, additional studies are needed to develop highly effective MCR targeted therapies that directly affect endogenous cells of the CNS, particularly OL, their progenitors and neurons.

show abstract

Section: Direct Effects In the Cnsmentioning

confidence: 99%

Section: Direct Effects In the Cnsmentioning

confidence: 99%

Melanocortins, Melanocortin Receptors and Multiple Sclerosis

Lisak

Benjamins

2017

Brain Sciences

View full text Add to dashboard Cite

show abstract

“…GAD67, glutamic acid decarboxylase; GFAP, anti-glial fibrillary acidic protein; GSK3β, glycogen synthase kinase 3β (Ser9 -inhibition, Tyr216 -activation); HF, high fat diet; Iba1, anti-ionized calciumbinding adaptor molecule 1; ICV, intracerebroventricular administration; i.n., intranasal; i.p., intraperitoneal; IRS- within the brain (Giuliani et al 2017). The neuroprotective properties of melanocortin agonists have been demonstrated in several models of neurodegeneration (Giuliani et al 2017). In different mouse models of AD-like pathology, such as in Tg2576 mice (Giuliani et al 2014b(Giuliani et al , 2015, TgCRND8 mice (Ma & McLaurin 2014) and in APP/PS1/P301L mice (Giuliani et al 2014a), intraperitoneal (i.p.)…”

Section: Journal Of Endocrinologymentioning

confidence: 99%

“…It has been suggested that some food intake-regulating peptides could be promising candidates for obesity and T2DM treatment , van der Klaauw 2018 and may also alleviate the cognitive deficits of neurodegenerative disorders (Giuliani et al 2017, Holscher 2018, Mandal et al 2018. Anorexigenic peptides lower food intake, while orexigenic peptides increase it.…”

Section: Introductionmentioning

confidence: 99%

The impact of anorexigenic peptides in experimental models of Alzheimer’s disease pathology

Maletı́nská

Popelová

Železná

et al. 2019

Journal of Endocrinology

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder in the elderly population. Numerous epidemiological and experimental studies have demonstrated that patients who suffer from obesity or type 2 diabetes mellitus have a higher risk of cognitive dysfunction and AD. Several recent studies demonstrated that food intake-lowering (anorexigenic) peptides have the potential to improve metabolic disorders and that they may also potentially be useful in the treatment of neurodegenerative diseases. In this review, the neuroprotective effects of anorexigenic peptides of both peripheral and central origins are discussed. Moreover, the role of leptin as a key modulator of energy homeostasis is discussed in relation to its interaction with anorexigenic peptides and their analogs in AD-like pathology. Although there is no perfect experimental model of human AD pathology, animal studies have already proven that anorexigenic peptides exhibit neuroprotective properties. This phenomenon is extremely important for the potential development of new drugs in view of the aging of the human population and of the significantly increasing incidence of AD.

show abstract

“…Pioneering studies by Caruso and colleagues revealed that central administration of α-MSH prevent the LPS-mediated induction of iNOS and COX 2 gene expression at the hypothalamic level, an effect that occurred via the activation of MC4Rs (Caruso et al, 2004). Similarly, agonists of MC4Rs counteract neuroinflammation and cell damage (Giuliani et al, 2006, 2014, 2017; Spaccapelo et al, 2011; Liu et al, 2015), whereas its pharmacological blockade or downregulation prevent the neuroprotective effects of α-MSH or its analogs and worse the outcome in different brain disease models (Giuliani et al, 2006; Zhang et al, 2015). While the neuroprotective actions of α-MSH/MC4R pathway are not completely understood, it has been proposed that they are in part exerted by inhibiting the production of inflammatory mediators from glial cells (Caruso et al, 2007).…”

Section: Neuroinflammation Oxidative Stress and Glia-to-neuron Miscmentioning

confidence: 99%

New Implications for the Melanocortin System in Alcohol Drinking Behavior in Adolescents: The Glial Dysfunction Hypothesis

Orellana

Cerpa

Carvajal

et al. 2017

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Alcohol dependence causes physical, social, and moral harms and currently represents an important public health concern. According to the World Health Organization (WHO), alcoholism is the third leading cause of death worldwide, after tobacco consumption and hypertension. Recent epidemiologic studies have shown a growing trend in alcohol abuse among adolescents, characterized by the consumption of large doses of alcohol over a short time period. Since brain development is an ongoing process during adolescence, short- and long-term brain damage associated with drinking behavior could lead to serious consequences for health and wellbeing. Accumulating evidence indicates that alcohol impairs the function of different components of the melanocortin system, a major player involved in the consolidation of addictive behaviors during adolescence and adulthood. Here, we hypothesize the possible implications of melanocortins and glial cells in the onset and progression of alcohol addiction. In particular, we propose that alcohol-induced decrease in α-MSH levels may trigger a cascade of glial inflammatory pathways that culminate in altered gliotransmission in the ventral tegmental area and nucleus accumbens (NAc). The latter might potentiate dopaminergic drive in the NAc, contributing to increase the vulnerability to alcohol dependence and addiction in the adolescence and adulthood.

show abstract

Multiple beneficial effects of melanocortin MC4 receptor agonists in experimental neurodegenerative disorders: Therapeutic perspectives

Cited by 30 publications

References 269 publications

Melanocortins, Melanocortin Receptors and Multiple Sclerosis

Melanocortins, Melanocortin Receptors and Multiple Sclerosis

The impact of anorexigenic peptides in experimental models of Alzheimer’s disease pathology

New Implications for the Melanocortin System in Alcohol Drinking Behavior in Adolescents: The Glial Dysfunction Hypothesis

Contact Info

Product

Resources

About