RESUMO
Purpose: The aim of the present work is the molecular diagnosis of three patients with deafness and retinal degeneration. Methods: Three patients from two unrelated families were initially analyzed with custom gene panels for Usher genes, non-syndromic hearing loss, or inherited syndromic retinopathies and further investigated by means of clinical or whole exome sequencing. Results: The study allowed us to detect likely pathogenic variants in PEX6, a gene typically involved in peroxisomal biogenesis disorders (PBDs). Beside deaf-blindness, both families showed additional features: Siblings from Family 1 showed enamel alteration and abnormal peroxisome. In addition, the brother had mild neurodevelopmental delay and nephrolithiasis. The case II:1 from Family 2 showed intellectual disability, enamel alteration, and dysmorphism. Conclusions: We have reported three new cases with pathogenic variants in PEX6 presenting with milder forms of the Zellweger spectrum disorders (ZSD). The three cases showed distinct clinical features. Thus, expanding the phenotypic spectrum of PBDs and ascertaining exome sequencing is an effective strategy for an accurate diagnosis of clinically overlapping and genetically heterogeneous disorders such as deafness-blindness association.
Assuntos
ATPases Associadas a Diversas Atividades Celulares/genética , Perda Auditiva Neurossensorial/genética , Retinose Pigmentar/genética , Síndrome de Zellweger/genética , Adulto , Criança , Anormalidades Craniofaciais/genética , Esmalte Dentário/anormalidades , Feminino , Humanos , Deficiência Intelectual/genética , Masculino , Mutação , Nefrolitíase/genética , Transtornos do Neurodesenvolvimento/genética , Linhagem , Peroxissomos/genética , Peroxissomos/metabolismo , Peroxissomos/patologia , Sequenciamento do ExomaRESUMO
Aging is characterized by the decline in many of the individual's capabilities. It has been recognized that the brain undergoes structural and functional changes during aging that are occasionally associated with the development of neurodegenerative diseases. In this sense, altered glutamatergic neurotransmission, which involves the release, binding, reuptake, and degradation of glutamate (Glu) in the brain, has been widely studied in physiological and pathophysiological aging. In particular, changes in glutamatergic neurotransmission are exacerbated during neurodegenerative diseases and are associated with cognitive impairment, characterized by difficulties in memory, learning, concentration, and decision-making. Thus, in the present manuscript, we aim to highlight the relevance of glutamatergic neurotransmission during cognitive impairment to develop novel strategies to prevent, ameliorate, or delay cognitive decline. To achieve this goal, we provide a comprehensive review of the changes reported in glutamatergic neurotransmission components, such as Glu transporters and receptors during physiological aging and in the most studied neurodegenerative diseases. Finally, we describe the current therapeutic strategies developed to target glutamatergic neurotransmission.
Assuntos
Envelhecimento , Disfunção Cognitiva , Ácido Glutâmico , Doenças Neurodegenerativas , Transmissão Sináptica , Humanos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/fisiopatologia , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Ácido Glutâmico/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologiaRESUMO
Aging is the result of the accumulation of a wide variety of molecular and cellular damages over time, meaning that "the more damage we accumulate, the higher the possibility to develop age-related diseases". Therefore, to reduce the incidence of such diseases and improve human health, it becomes important to find ways to combat such damage. In this sense, geroprotectors have been suggested as molecules that could slow down or prevent age-related diseases. On the other hand, nutraceuticals are another set of compounds that align with the need to prevent diseases and promote health since they are biologically active molecules (occurring naturally in food) that, apart from having a nutritional role, have preventive properties, such as antioxidant, anti-inflammatory and antitumoral, just to mention a few. Therefore, in the present review using the specialized databases Scopus and PubMed we collected information from articles published from 2010 to 2023 in order to describe the role of nutraceuticals during the aging process and, given their role in targeting the hallmarks of aging, we suggest that they are potential geroprotectors that could be consumed as part of our regular diet or administered additionally as nutritional supplements.