Parkinson's disease: Mechanisms, translational models and management strategies

Raza, Chand; Anjum, Rizwan; Shakeel, Noor ul Ain

doi:10.1016/j.lfs.2019.03.057

Cited by 409 publications

(322 citation statements)

References 182 publications

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“…Gene therapy has shown great progress in clinical trials over the last decade to face both inherited and acquired devastating brain diseases that do not have a reasonably effective treatment with conventional drugs (https://alliancerm.org/publication/q2-2019-data-report). In the case of inborn metabolism mutations of one gene that affect the brain, such as mucopolysaccharidoses or Canavan disease, the approach normally consists of the delivery of a functional copy of the gene to restore the normal phenothype [146][147][148]. However, in the case of brain-acquired diseases, where more than one gene can be affected, such as brain cancer, Alzheimer's, or Parkinson's diseases, the genetic approach is more challenging, since the molecular basis of those disorders are still not understood [148][149][150].…”

Section: General Conceptsmentioning

confidence: 99%

“…In the case of inborn metabolism mutations of one gene that affect the brain, such as mucopolysaccharidoses or Canavan disease, the approach normally consists of the delivery of a functional copy of the gene to restore the normal phenothype [146][147][148]. However, in the case of brain-acquired diseases, where more than one gene can be affected, such as brain cancer, Alzheimer's, or Parkinson's diseases, the genetic approach is more challenging, since the molecular basis of those disorders are still not understood [148][149][150]. BBB hampers the entry of gene expression vectors into the brain; consequently, gene treatments must be given after an invasive craniotomy, which in many cases jeopardizes the acceptance of patients enrolled in clinical trials due to the cumbersome approach and related side effects that increase the after-care cost as a consequence of additional hospital visits [151].…”

Section: General Conceptsmentioning

confidence: 99%

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Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues

et al. 2020

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Non-viral vectors have emerged as a promising alternative to viral gene delivery systems due to their safer profile. Among non-viral vectors, recently, niosomes have shown favorable properties for gene delivery, including low toxicity, high stability, and easy production. The three main components of niosome formulations include a cationic lipid that is responsible for the electrostatic interactions with the negatively charged genetic material, a non-ionic surfactant that enhances the long-term stability of the niosome, and a helper component that can be added to improve its physicochemical properties and biological performance. This review is aimed at providing recent information about niosome-based non-viral vectors for gene delivery purposes. Specially, we will discuss the composition, preparation methods, physicochemical properties, and biological evaluation of niosomes and corresponding nioplexes that result from the addition of the genetic material onto their cationic surface. Next, we will focus on the in situ application of such niosomes to deliver the genetic material into immune-privileged tissues such as the brain cortex and the retina. Finally, as future perspectives, non-invasive administration routes and different targeting strategies will be discussed.

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Section: General Conceptsmentioning

confidence: 99%

Section: General Conceptsmentioning

confidence: 99%

Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues

et al. 2020

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“…Some authors have studied the reliability of their instruments by examining whether they are able to detect the "off" vs. "on" change produced by the administration of levodopa and other antiparkinsonian drugs [30,31,42,43,46,50]. Theoretically, the rigidity responds well to medication [5,64], but frequently the outcome measures used (clinical scales such as UPDRS and others) in clinical trials seem to suffer from an obvious subjectivity, poor sensitivity to change, and variable inter-or intra-examiner reliability [5]. On the other hand, the use of instrumentalized methods could provide greater assurance regarding the efficacy of pharmacotherapy (and other treatments), since they offer quantitative information.…”

Section: Dopaminergic Medication and Rigiditymentioning

confidence: 99%

Quantitative Measurement of Rigidity in Parkinson’s Disease: A Systematic Review

Ferreira-Sánchez

Moreno-Verdú

Cano‐de‐la‐Cuerda

2020

Sensors

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Rigidity is one of the cardinal symptoms of Parkinson’s disease (PD). Present in up 89% of cases, it is typically assessed with clinical scales. However, these instruments show limitations due to their subjectivity and poor intra- and inter-rater reliability. To compile all of the objective quantitative methods used to assess rigidity in PD and to study their validity and reliability, a systematic review was conducted using the Web of Science, PubMed, and Scopus databases. Studies from January 1975 to June 2019 were included, all of which were written in English. The Strengthening the Reporting of observational studies in Epidemiology Statement (STROBE) checklist for observational studies was used to assess the methodological rigor of the included studies. Thirty-six studies were included. Rigidity was quantitatively assessed in three ways, using servomotors, inertial sensors, and biomechanical and neurophysiological study of muscles. All methods showed good validity and reliability, good correlation with clinical scales, and were useful for detecting rigidity and studying its evolution. People with PD exhibit higher values in terms of objective muscle stiffness than healthy controls. Rigidity depends on the angular velocity and articular amplitude of the mobilization applied. There are objective, valid, and reliable methods that can be used to quantitatively assess rigidity in people with PD.

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“…For this invasive treatment, PD patients must experience surgery again and again. It increases the risk of infection of the PD patients 6 . Currently available drugs or surgery are merely symptomatic treatments and do not slow down or prevent the progress of the disease.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of TO901317 on 6-OHDA-induced Parkinson rats in vitro and in vivo

Yang

Cheng

et al. 2020

Preprint

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Background: Stem cells from different sources could differentiate into dopamine-producing cells and ameliorate behavioral deficits in Parkinsonian models. Especially, human bone marrow mesenchymal stem cells (hBMSCs) have many advantages without ethical dispute. Liver X receptor s (LXRs) are involved in the maintenance of the normal function of the central nervous system myelin. We have reported the induction of cocktail-induced da phenotypes from adult rat BMSCs by using sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF) and TO901317 (agonist of LXRs) with 87.42% of efficiency in 6 days of period of induction. But the previous work did not verify whether the induced cells had the corresponding neural function. Methods: In this study, we demonstrated that TO901317 could promote the differentiation of hBMSCs into dopaminergic neurons. Neuronal markers (Tuj1, Neun and Nestin), dopamine neuron markers (tyrosine hydroxylase, TH), LXRa and LXRb were detected by immunofluorescence. RT-qPCR was used to measure the mRNA expressions of adenosine triphosphate-binding cassette transporter A1 (ABCA1). Western Blotting detected the changes of LXRa, LXRb and TH expression. Results: TO901317 significantly enhanced the differentiation from hBMSCs to DA neurons. Only the LXR+GF group released dopamine by the result of enzyme linked immunosorbent assay (ELISA). Compared with the control group and GF group, the optimal time for differentiation of hBMSCs treated by 0.5mM TO901317 combined with GF was six days. And the maximum induction efficiency was 91.67%. After transplanting induced-cells into Parkinson's disease rats, the symptoms of Parkinson's rats decreased, and the number of dopamine neurons increased in the substantia nigra and striatum. Conclusions: TO901317 promoted differentiation of hBMSCs into dopamine neurons may be related to activation of LXR-ABCA1 signaling pathway. These data suggest that TO901317 may serve as a potential therapeutic methods for Parkinson's disease.

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Parkinson's disease: Mechanisms, translational models and management strategies

Cited by 409 publications

References 182 publications

Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues

Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues

Quantitative Measurement of Rigidity in Parkinson’s Disease: A Systematic Review

Therapeutic effect of TO901317 on 6-OHDA-induced Parkinson rats in vitro and in vivo

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