Cerebellar Heterotopia: Broadening the Neuroradiological Spectrum of KBG Syndrome.

KBG syndrome is a rare genetic disorder caused by heterozygous pathogenic variants in ANKRD11. Affected individuals have developmental delay, short stature, characteristic facial features, and other dysmorphic findings. To date, a spectrum of unspecific neuroradiological defects has been reported in KBG patients, such as cortical defects, white matter abnormalities, corpus callosum, and cerebellar vermis hypoplasia.Deep clinical and neuroradiological phenotyping and genotype of a patient presenting with mild cognitive and behavioral problems were obtained after written informed consent.We herein describe the first KBG patient presenting with cerebellar heterotopia, a heterogeneous malformation characterized by the presence of clusters of neurons within the white matter of cerebellar hemispheres.This novel association broadens the neuroradiological spectrum of KBG syndrome, and further prompts to investigate the potential functions of ANKRD11 in cerebellar development.

The brain-gut-microbiota interplay in depression: A key to design innovative therapeutic approaches.

Depression is the most prevalent mental disorder in the world associated with huge socio-economic consequences. While depressive-related symptoms are well known, the molecular mechanisms underlying disease pathophysiology and progression remain largely unknown. The gut microbiota (GM) is emerging as a key regulator of the central nervous system homeostasis by exerting fundamental immune and metabolic functions. In turn, the brain influences the intestinal microbial composition through neuroendocrine signals, within the so-called gut microbiota-brain axis. The balance of this bidirectional crosstalk is important to ensure neurogenesis, preserve the integrity of the blood-brain barrier and avoid neuroinflammation. Conversely, dysbiosis and gut permeability negatively affect brain development, behavior, and cognition. Furthermore, although not fully defined yet, changes in the GM composition in depressed patients are reported to influence the pharmacokinetics of common antidepressants by affecting their absorption, metabolism, and activity. Similarly, neuropsychiatric drugs may shape in turn the GM with an impact on the efficacy and toxicity of the pharmacological intervention itself. Consequently, strategies aimed at re-establishing the correct homeostatic gut balance (i.e., prebiotics, probiotics, fecal microbiota transplantation, and dietary interventions) represent an innovative approach to improve the pharmacotherapy of depression. Among these, probiotics and the Mediterranean diet, alone or in combination with the standard of care, hold promise for clinical application. Therefore, the disclosure of the intricate network between GM and depression will give precious insights for innovative diagnostic and therapeutic approaches towards depression, with profound implications for drug development and clinical practice.

Non-Enzymatic Antioxidants against Alzheimer's Disease: Prevention, Diagnosis and Therapy.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Although substantial research has been conducted to elucidate the complex pathophysiology of AD, the therapeutic approach still has limited efficacy in clinical practice. Oxidative stress (OS) has been established as an early driver of several age-related diseases, including neurodegeneration. In AD, increased levels of reactive oxygen species mediate neuronal lipid, protein, and nucleic acid peroxidation, mitochondrial dysfunction, synaptic damage, and inflammation. Thus, the identification of novel antioxidant molecules capable of detecting, preventing, and counteracting AD onset and progression is of the utmost importance. However, although several studies have been published, comprehensive and up-to-date overviews of the principal anti-AD agents harboring antioxidant properties remain scarce. In this narrative review, we summarize the role of vitamins, minerals, flavonoids, non-flavonoids, mitochondria-targeting molecules, organosulfur compounds, and carotenoids as non-enzymatic antioxidants with AD diagnostic, preventative, and therapeutic potential, thereby offering insights into the relationship between OS and neurodegeneration.

The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence.

Cellular senescence is an irreversible state of cell cycle arrest occurring in response to stressful stimuli, such as telomere attrition, DNA damage, reactive oxygen species, and oncogenic proteins. Although beneficial and protective in several physiological processes, an excessive senescent cell burden has been involved in various pathological conditions including aging, tissue dysfunction and chronic diseases. Oxidative stress (OS) can drive senescence due to a loss of balance between pro-oxidant stimuli and antioxidant defences. Therefore, the identification and characterization of antioxidant compounds capable of preventing or counteracting the senescent phenotype is of major interest. However, despite the considerable number of studies, a comprehensive overview of the main antioxidant molecules capable of counteracting OS-induced senescence is still lacking. Here, besides a brief description of the molecular mechanisms implicated in OS-mediated aging, we review and discuss the role of enzymes, mitochondria-targeting compounds, vitamins, carotenoids, organosulfur compounds, nitrogen non-protein molecules, minerals, flavonoids, and non-flavonoids as antioxidant compounds with an anti-aging potential, therefore offering insights into innovative lifespan-extending approaches.

Blood-Based Biomarkers for Alzheimer's Disease Diagnosis and Progression: An Overview.

Alzheimer's Disease (AD) is a progressive neurodegenerative disease characterized by amyloid-ß (Aß) plaque deposition and neurofibrillary tangle accumulation in the brain. Although several studies have been conducted to unravel the complex and interconnected pathophysiology of AD, clinical trial failure rates have been high, and no disease-modifying therapies are presently available. Fluid biomarker discovery for AD is a rapidly expanding field of research aimed at anticipating disease diagnosis and following disease progression over time. Currently, Aß1-42, phosphorylated tau, and total tau levels in the cerebrospinal fluid are the best-studied fluid biomarkers for AD, but the need for novel, cheap, less-invasive, easily detectable, and more-accessible markers has recently led to the search for new blood-based molecules. However, despite considerable research activity, a comprehensive and up-to-date overview of the main blood-based biomarker candidates is still lacking. In this narrative review, we discuss the role of proteins, lipids, metabolites, oxidative-stress-related molecules, and cytokines as possible disease biomarkers. Furthermore, we highlight the potential of the emerging miRNAs and long non-coding RNAs (lncRNAs) as diagnostic tools, and we briefly present the role of vitamins and gut-microbiome-related molecules as novel candidates for AD detection and monitoring, thus offering new insights into the diagnosis and progression of this devastating disease.