Non-canonical pathways associated to Amyloid beta and tau protein dyshomeostasis in Alzheimer's disease: A narrative review.

Alzheimer's Disease (AD) is the most common form of dementia among elderly people. This disease imposes a significant burden on the healthcare system, society, and economy due to the increasing global aging population. Current trials with drugs or bioactive compounds aimed at reducing cerebral Amyloid beta (Aβ) plaques and tau protein neurofibrillary tangles, which are the two main hallmarks of this devastating neurodegenerative disease, have not provided significant results in terms of their neuropathological outcomes nor met the expected clinical end-points.

Human NGF "Painless" Ocular Delivery for Retinitis Pigmentosa: An In Vivo Study.

Retinitis pigmentosa (RP) is a family of genetically heterogeneous diseases still without a cure. Despite the causative genetic mutation typically not expressed in cone photoreceptors, these cells inevitably degenerate following the primary death of rods, causing blindness. The reasons for the "bystander" degeneration of cones are presently unknown but decrement of survival factors, oxidative stress, and inflammation all play a role.

Cognitive, Neuropsychological and Biological Effects of Oxygen-Ozone Therapy on Frailty: A Study Protocol for a 5-Week, Randomized, Placebo-Controlled Trial.

Cognitive frailty (CF) is a heterogeneous syndrome that is becoming one of the most serious health problems as the world's population age is increasing. Elucidating its biological mechanisms as well as prevention and treatments is becoming increasingly significant, particularly in view of the associated health costs. We presented the study protocol of a research project funded by the Italian Ministry of Health (grant number RF-2016-02363298) aiming to investigate the cognitive and neuropsychological effects of a 5-week treatment with therapy based on the regenerative properties of ozone (O) in a cohort of subjects stratified according to CF scores.

miR-92a-3p and miR-320a are Upregulated in Plasma Neuron-Derived Extracellular Vesicles of Patients with Frontotemporal Dementia.

Despite the efforts to identify fluid biomarkers to improve diagnosis of Frontotemporal dementia (FTD), only a few candidates have been described in recent years. In a previous study, we identified three circulating miRNAs (miR-92a-3p, miR-320a and miR-320b) differentially expressed in FTD patients with respect to healthy controls and/or Alzheimer's disease (AD) patients. Now, we investigated whether those changes could be due to miRNAs contained in neuron-derived extracellular vesicles (NDEVs).

Pathological Defects in a Drosophila Model of Alzheimer's Disease and Beneficial Effects of the Natural Product Lisosan G.

Alzheimer's disease (AD) brains are histologically marked by the presence of intracellular and extracellular amyloid deposits, which characterize the onset of the disease pathogenesis. Increasing evidence suggests that certain nutrients exert a direct or indirect effect on amyloid β (Aβ)-peptide production and accumulation and, consequently, on AD pathogenesis. We exploited the fruit fly model of AD to evaluate in vivo the beneficial properties of Lisosan G, a fermented powder obtained from organic whole grains, on the intracellular Aβ-42 peptide accumulation and related pathological phenotypes of AD.

Essential role of p21 in the modulation of post-traumatic hippocampal Neural Stem Cells response.

Background: Traumatic Brain Injury (TBI) represents one of the main causes of brain damage in young people and the elderly population with a very high rate of psycho-physical disability and death. TBI is characterized by extensive cell death, tissue damage and neuro-inflammation with a symptomatology that varies depending on the severity of the trauma from memory loss to a state of irreversible coma and death. Recently, preclinical studies on mouse models have demonstrated that the post-traumatic adult Neural Stem/Progenitor cells response could represent an excellent model to shed light on the neuro-reparative role of adult neurogenesis following damage.

Exploring miRNAs' Based Modeling Approach for Predicting PIRA in Multiple Sclerosis: A Comprehensive Analysis.

The current hypothesis on the pathophysiology of multiple sclerosis (MS) suggests the involvement of both inflammatory and neurodegenerative mechanisms. Disease Modifying Therapies (DMTs) effectively decrease relapse rates, thus reducing relapse-associated disability in people with MS. In some patients, disability progression, however, is not solely linked to new lesions and clinical relapses but can manifest independently.

miR-218-5p and doxorubicin combination enhances anticancer activity in breast cancer cells through Parkin-dependent mitophagy inhibition.

Breast Cancer (BC) is one of the most common tumours, and is known for its ability to develop resistance to chemotherapeutic treatments. Autophagy has been linked to chemotherapeutic response in several types of cancer, highlighting its contribution to this process. However, the role of mitophagy, a selective form of autophagy responsible for damaged mitochondria degradation, in the response to therapies in BC is still unclear.

Cerebrospinal fluid level of proNGF as potential diagnostic biomarker in patients with frontotemporal dementia.

Introduction: Frontotemporal dementia (FTD) is an extremely heterogeneous and complex neurodegenerative disease, exhibiting different phenotypes, genetic backgrounds, and pathological states. Due to these characteristics, and to the fact that clinical symptoms overlap with those of other neurodegenerative diseases or psychiatric disorders, the diagnosis based only on the clinical evaluation is very difficult. The currently used biomarkers help in the clinical diagnosis, but are insufficient and do not cover all the clinical needs.

Insulin-like growth factor 2 (IGF-2) rescues social deficits in NLG3 mouse model of ASDs.

Autism spectrum disorders (ASDs) comprise developmental disabilities characterized by impairments of social interaction and repetitive behavior, often associated with cognitive deficits. There is no current treatment that can ameliorate most of the ASDs symptomatology; thus, identifying novel therapies is urgently needed. Here, we used the Neuroligin 3 knockout mouse (NLG3), a model that recapitulates the social deficits reported in ASDs patients, to test the effects of systemic administration of IGF-2, a polypeptide that crosses the blood-brain barrier and acts as a cognitive enhancer.

Cladribine and ocrelizumab induce differential miRNA profiles in peripheral blood mononucleated cells from relapsing-remitting multiple sclerosis patients.

Background And Objectives: Multiple sclerosis (MS) is a chronic, progressive neurological disease characterized by early-stage neuroinflammation, neurodegeneration, and demyelination that involves a spectrum of heterogeneous clinical manifestations in terms of disease course and response to therapy. Even though several disease-modifying therapies (DMTs) are available to prevent MS-related brain damage-acting on the peripheral immune system with an indirect effect on MS lesions-individualizing therapy according to disease characteristics and prognostic factors is still an unmet need. Given that deregulated miRNAs have been proposed as diagnostic tools in neurodegenerative/neuroinflammatory diseases such as MS, we aimed to explore miRNA profiles as potential classifiers of the relapsing-remitting MS (RRMS) patients' prospects to gain a more effective DMT choice and achieve a preferential drug response.

COVID-19 and Alzheimer's Disease Share Common Neurological and Ophthalmological Manifestations: A Bidirectional Risk in the Post-Pandemic Future.

A growing body of evidence indicates that a neuropathological cross-talk takes place between the coronavirus disease 2019 (COVID-19) -the pandemic severe pneumonia that has had a tremendous impact on the global economy and health since three years after its outbreak in December 2019- and Alzheimer's Disease (AD), the leading cause of dementia among human beings, reaching 139 million by the year 2050. Even though COVID-19 is a primary respiratory disease, its causative agent, the so-called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), is also endowed with high neuro-invasive potential (Neurocovid). The neurological complications of COVID-19, resulting from the direct viral entry into the Central Nervous System (CNS) and/or indirect systemic inflammation and dysregulated activation of immune response, encompass memory decline and anosmia which are typically associated with AD symptomatology.

Transcriptome analysis reveals genes associated with stem cell activation by physical exercise in the dentate gyrus of aged p16Ink4a knockout mice.

Throughout adulthood neural stem cells divide in neurogenic niches-the dentate gyrus of the hippocampus and the subventricular zone-producing progenitor cells and new neurons. Stem cells self-renew, thus preserving their pool. Furthermore, the number of stem/progenitor cells in the neurogenic niches decreases with age.

From cardiovascular system to brain, the potential protective role of Mas Receptors in COVID-19 infection.

Coronavirus disease 2019 (COVID-19) has been declared a new pandemic in March 2020. Although most patients are asymptomatic, those with underlying cardiovascular comorbidities may develop a more severe systemic infection which is often associated with fatal pneumonia. Nonetheless, neurological and cardiovascular manifestations could be present even without respiratory symptoms.

GABA Signaling: Therapeutic Targets for Neurodegenerative and Neurodevelopmental Disorders.

This Special Issue, "GABA Signaling: Therapeutic Targets for Neurodegenerative and Neurodevelopmental Disorders", focuses on a fundamental property of the neurotransmitter γ-aminobutyric acid (GABA), namely its capacity to shift, in particular conditions, from the hyperpolarizing to the depolarizing direction [...

Transcriptomic Analysis in the Hippocampus and Retina of Tg2576 AD Mice Reveals Defective Mitochondrial Oxidative Phosphorylation and Recovery by Tau 12A12mAb Treatment.

Increasing evidence implicates decreased energy metabolism and mitochondrial dysfunctions among the earliest pathogenic events of Alzheimer's disease (AD). However, the molecular mechanisms underlying bioenergetic dysfunctions in AD remain, to date, largely unknown. In this work, we analyzed transcriptomic changes occurring in the hippocampus and retina of a Tg2576 AD mouse model and wild-type controls, evaluating their functional implications by gene set enrichment analysis.

Plasma Biomarker Profile and Clinical Correlations in Adult Patients With Tuberous Sclerosis Complex.

Objectives: Different pathophysiologic mechanisms, especially involving astrocytes, could contribute to tuberous sclerosis complex (TSC). We assessed neurodegeneration and astrocytopathy plasma biomarkers in adult patients with TSC to define TSC biomarker profile and investigate clinical-radiologic correlations.

Methods: Patients with TSC aged 15 years or older followed at Policlinico "Umberto I" of Rome were consecutively enrolled (July 2021-June 2022).

Reversal of neurological deficits by painless nerve growth factor in a mouse model of Rett syndrome.

Rett syndrome is a rare genetic neurodevelopmental disease, affecting 1 in over 10 000 females born worldwide, caused by de novo mutations in the X-chromosome-located methyl-CpG-binding protein 2 (MeCP2) gene. Despite the great effort put forth by the scientific community, a therapy for this devastating disease is still needed. Here, we tested the therapeutic effects of a painless mutein of the nerve growth factor (NGF), called human NGF painless (hNGFp), via a non-invasive intranasal delivery in female MeCP2+/- mice.

An ontology-based approach for modelling and querying Alzheimer's disease data.

Background: The recent advances in biotechnology and computer science have led to an ever-increasing availability of public biomedical data distributed in large databases worldwide. However, these data collections are far from being "standardized" so to be harmonized or even integrated, making it impossible to fully exploit the latest machine learning technologies for the analysis of data themselves. Hence, facing this huge flow of biomedical data is a challenging task for researchers and clinicians due to their complexity and high heterogeneity.

Novel loss of function mutation in gene compromises tubulin stability and proteostasis causing spastic paraplegia and ataxia.

Microtubules are dynamic cytoskeletal structures involved in several cellular functions, such as intracellular trafficking, cell division and motility. More than other cell types, neurons rely on the proper functioning of microtubules to conduct their activities and achieve complex morphologies. Pathogenic variants in genes encoding for α and β-tubulins, the structural subunits of microtubules, give rise to a wide class of neurological disorders collectively known as "tubulinopathies" and mainly involving a wide and overlapping range of brain malformations resulting from defective neuronal proliferation, migration, differentiation and axon guidance.

The ferroptosis inducer RSL3 triggers interictal epileptiform activity in mice cortical neurons.

Epilepsy is a neurological disorder characterized by recurrent seizures, which result from excessive, synchronous discharges of neurons in different brain areas. In about 30% of cases, epileptic discharges, which vary in their etiology and symptomatology, are difficult to treat with conventional drugs. Ferroptosis is a newly defined iron-dependent programmed cell death, characterized by excessive accumulation of lipid peroxides and reactive oxygen species.

The Cleavage-Specific Tau 12A12mAb Exerts an Anti-Amyloidogenic Action by Modulating the Endocytic and Bioenergetic Pathways in Alzheimer's Disease Mouse Model.

Beyond deficits in hippocampal-dependent episodic memory, Alzheimer's Disease (AD) features sensory impairment in visual cognition consistent with extensive neuropathology in the retina. 12A12 is a monoclonal cleavage specific antibody (mAb) that in vivo selectively neutralizes the AD-relevant, harmful N-terminal 20-22 kDa tau fragment(s) (i.e.

Plasma ATN(I) classification and precision pharmacology in Alzheimer's disease.

Evaluating potential therapies for Alzheimer's disease (AD) depends on use of biomarkers for appropriate subject selection and monitoring disease progression. Biomarkers that predict onset of clinical symptoms are particularly important for AD because they enable intervention before irreversible neurodegeneration occurs. The amyloid-β-tau-neurodegeneration (ATN) classification system is currently used as a biological staging model for AD and is based on three classes of biomarkers evaluating amyloid-β (Aβ), tau pathology and neurodegeneration or neuronal injury.