Carnosine is a naturally occurring endogenous dipeptide composed by the ligation of β-alanine and L-histidine performed particularly by tissues with an increased oxidative metabolism such as muscles and brain. In the last 50 years different studies have assessed the role and function of carnosine through numerous in vitro, in vivo, and clinical studies, demonstrating the multimodal mechanism of action of this dipeptide that includes anti-aggregant, antioxidant, and anti-inflammatory activities. In particular its activity has been investigated in experimental models of cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and neurodegenerative disorders, such as cerebral ischemia and Alzheimer's disease (AD). In the present review, we examined the protective role that carnosine could exert in the context of T2DM, CVD, and AD, which show common pathogenic mechanisms including oxidative stress, inflammation, and aggregation phenomena. Carnosine's pharmacodynamic profile is multimodal and combines the systemic anti-inflammatory and antioxidant activities with its anti-aggregant and neuroprotective efficacy in the central nervous system. This enlarged pharmacological activity opens a new path to explore the therapeutic potential of carnosine in all the three diseases, and in particular in patients with T2DM, who often show a history of CVD and also have an increased risk to develop mild cognitive impairment and AD.

Microglia represent the immune system of the brain. Their role is central in two phenomena, neuroinflammation and oxidative stress, which are at the roots of different pathologies related to the central nervous system (CNS). In order to maintain the homeostasis of the brain and re-establish the equilibrium after a threatening imbalance, microglia communicate with each other and other cells within the CNS by receiving specific signals through membrane-bound receptors and then releasing neurotrophic factors into either the extracellular milieu or directly into the cytoplasm of nearby cells, such as astrocytes and neurons. These last two mechanisms rely on the activity of protein structures that enable the formation of channels in the membrane, namely, connexins and pannexins, that group and form gap junctions, hemichannels, and pannexons. These channels allow the release of gliotransmitters, such as adenosine triphosphate (ATP) and glutamate, together with calcium ion (Ca²⁺), that seem to play a pivotal role in inter-cellular communication. The aim of the present review is focused on the physiology of channel protein complexes and their contribution to neuroinflammatory and oxidative stress-related phenomena, which play a central role in neurodegenerative disorders. We will then discuss how pharmacological modulation of these channels can impact neuroinflammatory phenomena and hypothesize that currently available nutraceuticals, such as carnosine and N-acetylcysteine, can modulate the activity of connexins and pannexins in microglial cells and reduce oxidative stress in neurodegenerative disorders.

Carnosine is an endogenous dipeptide composed of β-alanine and L-histidine, possessing a multimodal pharmacodynamic profile that includes anti-inflammatory and anti-oxidant activities. Carnosine has also shown its ability to modulate cell proliferation, cell cycle arrest, apoptosis, and even glycolytic energy metabolism, all processes playing a key role in the context of cancer. Cancer is one of the most dreaded diseases of the 20th and 21st centuries. Among the different types of cancer, breast cancer represents the most common non-skin cancer among women, accounting for an estimated 15% of all cancer-related deaths in women. The main aim of the present review was to provide an overview of studies on the anti-cancer activity of carnosine, and in particular its activity against breast cancer. We also highlighted the possible advantages and limitations involved in the use of this dipeptide. The first part of the review entailed a brief description of carnosine’s biological activities and the pathophysiology of cancer, with a focus on breast cancer. The second part of the review described the anti-tumoral activity of carnosine, for which numerous studies have been carried out, especially at the preclinical level, showing promising results. However, only a few studies have investigated the therapeutic potential of this dipeptide for breast cancer prevention or treatment. In this context, carnosine has shown to be able to decrease the size of cancer cells and their viability. It also reduces the levels of vascular endothelial growth factor (VEGF), cyclin D1, NAD⁺, and ATP, as well as cytochrome c oxidase activity in vitro. When tested in mice with induced breast cancer, carnosine proved to be non-toxic to healthy cells and exhibited chemopreventive activity by reducing tumor growth. Some evidence has also been reported at the clinical level. A randomized phase III prospective placebo-controlled trial showed the ability of Zn–carnosine to prevent dysphagia in breast cancer patients undergoing adjuvant radiotherapy. Despite this evidence, more preclinical and clinical studies are needed to better understand carnosine’s anti-tumoral activity, especially in the context of breast cancer.

The burden of increasing cancer incidence among the population, and, in particular, of prostate cancer in men living in highly developed countries, brings with it, on one hand, the need for new devices that allow a faster and earlier diagnosis, ideally in a non-invasive way and with low consumption of expensive reagents, and on the other the need for the assessment of new in vitro models that allow a more reliable assessment of cancer features, including its microenvironment and sensibility to different drugs. At the crossroads of these features, microfluidic devices are found. These, taking advantage of the chemical-physical properties of cells and human samples, have demonstrated great sensitivity and sensibility at an on-chip scale. Many fields of biomedical sciences have tried to exploit all their potentialities: from the detection of antigens in the early phases of the disease (when they are very low concentrated, but the treatment is more effective) to isolation and characterization of circulating tumor cells. However, is in the building of in vitro 3D models to better assess and comprehend the fundamental dynamics occurring in the tumor microenvironment and metastasis that 3D bioprinting techniques come into play. The aim of the present review is to describe the potential of these two different cutting-edge technologies for the detection and treatment of prostate cancer, in the perspective of a possible future combination of them that allows scientists to fill the gaps present in the field to improve patient care and treatment.

Endometriosis is a chronic pathological condition characterized by the growth of endometrial-like tissue outside the uterine cavity and is frequently associated with severe pain, persistent inflammation, and fibrosis within the pelvic region and other parts of the body. The exact causes of endometriosis are not clear, but an innate or adaptive immune response defect has recently been suggested as a factor in the disease’s development. Carnosine is a natural dipeptide formed by the ligation of β-alanine and L-histidine and characterized by a multimodal mechanism of action that includes antioxidant and anti-inflammatory activities. Carnosine has also been shown to modulate glucose, nucleotide, and lipid metabolism as well as the response of immune cells, all processes that play a key role in the context of endometriosis. Despite numerous reviews published on the structure, role, function, and biological activities of carnosine in preclinical and clinical settings, none have focused on its therapeutic potential for the prevention or treatment of reproductive disorders, including endometriosis. In this review, after a brief introduction to the pathogenesis and pathophysiology of endometriosis, we focus on the use of carnosine for the management of reproductive disorders, concluding with its ability to modulate specific cellular and molecular mechanisms closely related to endometriosis. Given the central role of oxidative stress and inflammation across several reproductive disorders, carnosine may represent a promising therapeutic candidate not only in endometriosis, but also in broader reproductive health contexts.