An update on the diagnosis and treatment of Parkinson disease

Rizek, Philippe; Kumar, Niraj; Jog, Mandar

doi:10.1503/cmaj.151179

Cited by 349 publications

(270 citation statements)

References 117 publications

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“…Bestetik, antikolinergikoak (proziklidina, biperidenoa, trihexifenidiloa), azetilkolinak dopaminaren efektuak antagonizatzen ditu eta. Bere eragin kaltegarriak aintzat hartuta ez dira adineko pertsonengan gomendagarriak, baina paziente gazteentzat erabil daitezke zurruntasuna eta distonia nagusitzen direnean [12].…”

Section: Maialen Duque Ainhoa Sagarduy Jorge E Ortega Teresa Moreunclassified

Aurrerapen terapeutikoak Parkinson gaixotasunean

Duque

Sagarduy

Ortega

et al. 2020

EKAIA

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Parkinson gaixotasuna (PG) adinarekin erlazionatutako gaixotasun neurodegeneratiboa da. PGren prebalentzia gorantz doa, eta hurrengo 40 urteetan kasuak bikoiztuko direla uste da. Gaur egun, farmako erabilgarrien artean, L-dopak tratamendurik eraginkorrena izaten jarraitzen du, baina ez du endekapena geldiarazten edo moteltzen. Horrez gain, denbora pasatu ahala, haren eraginkortasuna murriztu egiten da, eta ondorio kaltegarriak eragiten ditu: esate baterako, diskinesiak. Berrikuspen honek PG tratatzeko aurrerapen terapeutiko berriak laburbiltzen ditu; besteak beste, farmako serotonergikoak eta glutamatergikoak, farmakozinetika hobetzeko forma farmazeutikoak edo garezurrean zeharreko estimulazio magnetikoa.

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Section: Maialen Duque Ainhoa Sagarduy Jorge E Ortega Teresa Moreunclassified

Aurrerapen terapeutikoak Parkinson gaixotasunean

Duque

Sagarduy

Ortega

et al. 2020

EKAIA

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“…Despite these research efforts of the last decades that identified a wealth of candidate molecular readouts, there is no single reliable biomarker available yet that provides clinical utility for diagnosing or prognosing PD (76). This issue may largely result from the relatively low prevalence of PD on which sensitivity, specificity, and the predictive values of these measures are dependent (77) and has been discussed before (78)(79)(80).…”

Section: Molecular Markers Of Parkinson's Diseasementioning

confidence: 99%

The Challenge and Opportunity to Diagnose Parkinson's Disease in Midlife

et al. 2019

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Parkinson's disease (PD) is the most common neurodegenerative movement disorder that affects extensive regions of the nervous system. Its current clinical diagnosis is based on motor symptoms that appear late during disease progression when substantial proportions of the nigrostriatal dopaminergic neuron population are lost already. Although disturbances in sleep and other biofunctions often surface years prior to motor impairments and point to a long prodromal phase, these phenotypic signs in a person's midlife lack predictive power. They do, however, signal the unfolding of the disease and suggest molecular correlates that begin deviating early on. Revealing such trajectories, hence, promises not only a better understanding of prodromal PD but may also enable a much-needed earlier diagnosis. A nexus that may harbor such molecular trajectories is the epigenome as key etiological factors of PD-genetics, age, and environment-influence this substrate. An earlier diagnosis would also allow earlier interventions and lifestyle adjustments to improve brain function and reduce symptoms. In this review, we describe the challenges of diagnosing PD early on and highlight the opportunities that may arise from steering research efforts towards comprehensive interrogations of molecular layers during the long-time neglected midlife phase. In particular, we emphasize how existing cohorts of at-risk individuals, available animal models, and suitable markers may come together and aid in revealing molecular trajectories that offer diagnostic utility for PD in its prodromal stage.

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“…This disease causes reduced dopamine production due to progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta and accumulation of cytoplasmic inclusions (Lewy bodies) mainly composed of misfolded αsynuclein (α-syn), a protein prone to self-aggregation and toxicity 2,3 . Current therapies are symptomatic rather than restorative and aim to raise dopamine levels in the brain 4 .…”

Section: Introductionmentioning

confidence: 99%

Hydrogel-based delivery of Tat-fused protein Hsp70 protects dopaminergic cells in vitro and in a mouse model of Parkinson’s disease

et al. 2019

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Neurodegenerative disorders such as Parkinson's disease (PD) have no effective therapies. However, many promising drugs are precluded from clinical trials because of their poor brain availability. The chaperone protein Hsp70 has been reported to be effective in PD models, but its brain targeting is challenging. We developed a novel brain Hsp70 delivery system using injectable, biocompatible, and biodegradable semi-interpenetrating polymer networks of collagen (COLL) and low-molecular-weight hyaluronic acid (LMW HA) structured with gelatin particles. We produced human recombinant Hsp70-1A fused with the cell-penetrating peptide Tat (Tat-Hsp70) that was neuroprotective in vitro against the dopaminergic toxin 6-hydroxydopamine (6-OHDA). We assessed Tat-Hsp70 release from the selected COLL-LMW HA composites in vitro, observing a 95% release of loaded protein after 96 h. The release kinetics FITTED the Korsmeyer-Peppas model (regression coefficient 0.98) and the released Tat-Hsp70 remained neuroprotective for SH-SY5Y cells. Magnetic resonance imaging revealed that COLL-LMW HA composites lasted at least 96 h at the brain level, and in vivo Tat-Hsp70 release studies indicated that hydrogel presence is pivotal for a spatially focused neuroprotective effect. In an in vivo model of dopaminergic degeneration, Tat-Hsp70-loaded composites conveyed neuroprotection at both the behavioral and dopaminergic neuronal levels against the striatal injection of 6-OHDA. After the injection of Tat-Hsp70-loaded composites, mice showed a transient inflammatory response, with a decrease in GFAP and CD11b immunostaining after 7 days. Our delivery system enabled the effective brain release of Tat-Hsp70 and is ready for further improvements.

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An update on the diagnosis and treatment of Parkinson disease

Cited by 349 publications

References 117 publications

Aurrerapen terapeutikoak Parkinson gaixotasunean

Aurrerapen terapeutikoak Parkinson gaixotasunean

The Challenge and Opportunity to Diagnose Parkinson's Disease in Midlife

Hydrogel-based delivery of Tat-fused protein Hsp70 protects dopaminergic cells in vitro and in a mouse model of Parkinson’s disease

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