RESUMO
The technique of gene therapy, ever since its advent nearly fifty years ago, has been utilized by scientists as a potential treatment option for various disorders. This review discusses some of the major neurodegenerative diseases (NDDs) like Alzheimer's disease (AD), Parkinson's Disease (PD), Motor neuron diseases (MND), Spinal Muscular Atrophy (SMA), Huntington's Disease (HD), Multiple Sclerosis (MS), etc. and their underlying genetic mechanisms along with the role that gene therapy can play in combating them. The pathogenesis and the molecular mechanisms specifying the altered gene expression of each of these NDDs have also been discussed in elaboration. The use of gene therapy vectors can prove to be an effective tool in the field of curative modern medicine for the generations to come. Therefore, consistent efforts and progressive research towards its implementation can provide us with powerful treatment options for disease conditions that have so far been considered as incurable.
Assuntos
Sistemas de Liberação de Medicamentos , Edição de Genes/métodos , Regulação da Expressão Gênica , Terapia Genética , Vetores Genéticos , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/terapia , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/terapia , Humanos , Doença de Huntington/genética , Doença de Huntington/terapia , Doença dos Neurônios Motores/genética , Doença dos Neurônios Motores/terapia , Esclerose Múltipla/genética , Esclerose Múltipla/terapia , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/terapia , Doença de Parkinson/genética , Doença de Parkinson/terapia , Doenças Retinianas/genética , Doenças Retinianas/terapiaRESUMO
In recent times, several approaches for targeted gene therapy (GT) had been studied. However, the emergence of extracellular vesicles (EVs) as a shuttle carrying genetic information between cells has gained a lot of interest in scientific communities. Owing to their higher capabilities in dealing with short sequences of nucleic acid (mRNA, miRNA), proteins, recombinant proteins, exosomes, the most popular form of EVs are viewed as reliable biological therapeutic conveyers. They have natural access through every biological membrane and can be employed for site-specific and efficient drug delivery without eliciting any immune responses hence, qualifying as an ideal delivery vehicle. Also, there are many research studies conducted in the last few decades on using exosome-mediated gene therapy into developing an effective therapy with the concept of a higher degree of precision in gene isolation, purification and delivery mechanism loading, delivery and targeting protocols. This review discusses several facets that contribute towards developing an efficient therapeutic regime for gene therapy, highlighting limitations and drawbacks associated with current GT and suggested therapeutic regimes.
Assuntos
Sistemas de Liberação de Medicamentos/tendências , Exossomos/genética , Técnicas de Transferência de Genes/tendências , Terapia Genética , Exossomos/ultraestrutura , Vesículas Extracelulares/genética , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêuticoRESUMO
Locating remedies for Alzheimer's disease (AD) has been majorly restricted by the inefficiency to establish a definitive detection model for early-stage diagnosis of pathological events. This current lapse in AD diagnosis also limits the therapeutic efficiency of the drugs, which might have been effective if given at the earlier stages of the disease. The indicated situation directs towards the burgeoned need for an effective biomarker technique that will help in early detection of AD and would be imminently useful to facilitate improved diagnosis and stimulate therapeutic trials. Till date, the major biomarkers, specifically associated with AD detection, may help in determining the early-stage AD diagnosis and identifying alterations in the cellular proteome, offering deeper insight into disease etiology. Currently existing multidisciplinary clinical diagnosis of AD is a very tedious, expensive procedure and requires highly trained and skilled professionals who are rarely available outside the specialty clinics. Mutations in amyloid precursor protein (APP) or Presenilin 1 and 2 (PSEN1 and PSEN2) are some biomarkers acting as critical checkpoints for AD diagnosis. However, the presence of some associated biomarkers in cerebrospinal fluid (CSF) such as total-Tau (tTau), phosphorylated- Tau (pTau) 181 and Amyloid-ß (Aß) 1-42 using structural or functional imaging techniques is considered for confirmatory diagnosis of AD. Furthermore, the molecular diagnosis of AD incorporates various sophisticated techniques including immuno-sensing, machine learning, nano conjugation-based detections, etc. In the current review description, we have summarized the various diagnostic approaches and their relevance in mitigating the long-standing urgency of targeted diagnostic tools for detection of AD.
Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Demência/genética , Testes Diagnósticos de Rotina , Proteômica/métodos , Proteínas tau/genética , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/metabolismo , Biomarcadores/metabolismo , Demência/diagnóstico , Demência/metabolismo , Demência/patologia , Regulação da Expressão Gênica , Humanos , Imunoensaio , Neurogranina/genética , Neurogranina/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Fosforilação , Presenilina-1/genética , Presenilina-1/metabolismo , Presenilina-2/genética , Presenilina-2/metabolismo , Transdução de Sinais , Proteínas tau/metabolismoRESUMO
Alzheimer's disease (AD), a progressively fatal neurodegenerative disorder, is the most prominent form of dementia found today. Patients suffering from Alzheimer's begin to show the signs and symptoms, like decline in memory and cognition, long after the cellular damage has been initiated in their brain. There are several hypothesis for the neurodegeneration process; however, the lack of availability of in vivo models makes the recapitulation of AD in humans impossible. Moreover, the drugs currently available in the market serve to alleviate the symptoms and there is no cure for the disease. There have been two major hurdles in the process of finding the same-the inefficiency in cracking the complexity of the disease pathogenesis and the inefficiency in delivery of drugs targeted for AD. This review discusses the different drugs that have been designed over the recent years and the drug delivery options in the field of nanotechnology that have been found most feasible in surpassing the blood-brain barrier (BBB) and reaching the brain.
