Pharmacological Treatment of Parkinson’s Disease

Zahoor, Insha; Shafi, Amrina; Haq, Ehtishamul

doi:10.15586/codonpublications.parkinsonsdisease.2018.ch7

Cited by 73 publications

(65 citation statements)

References 60 publications

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“…The most used therapeutic approach to alleviate parkinsonian motor symptoms is the administration of DA precursor, levodopa (L-DOPA; Nutt, 1999 ; Fahn, 2000 , 2015 ; Obeso et al, 2000 , 2017 ; Olanow and Schapira, 2013 ; Espay et al, 2018 ). The striatum is considered the main target of L-DOPA, which efficiently provides a restoration of the concentrations of DA (Cotzias et al, 1967 ; Birkmayer and Hornykiewicz, 1998 ; Fahn, 2015 ; Zahoor et al, 2018 ). Besides its antiparkinsonian effects, however, long-term use of L-DOPA causes, in most patients, motor fluctuations and involuntary hyperkinetic movements (i.e., dyskinesia; Calabresi et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Rapamycin, by Inhibiting mTORC1 Signaling, Prevents the Loss of Striatal Bidirectional Synaptic Plasticity in a Rat Model of L-DOPA-Induced Dyskinesia

Calabrese

Maio

Marino

et al. 2020

Front. Aging Neurosci.

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Levodopa (L-DOPA) treatment is the main gold-standard therapy for Parkinson disease (PD). Besides good antiparkinsonian effects, prolonged use of this drug is associated to the development of involuntary movements known as L-DOPA-induced dyskinesia (LID). L-DOPA-induced dyskinesia is linked to a sensitization of dopamine (DA) D1 receptors located on spiny projection neurons (SPNs) of the dorsal striatum. Several evidences have shown that the emergence of LID can be related to striatal D1/cAMP/PKA/DARPP-32 and extracellular signal-regulated kinases (ERK1/2) pathway overactivation associated to aberrant N-methyl-d-aspartate (NMDA) receptor function. In addition, within striatum, ERK1/2 is also able to modulate in a D1 receptor-dependent manner the activity of the mammalian target of rapamycin complex 1 (mTORC1) pathway under DA depletion and L-DOPA therapy. Consistently, increased mTORC1 signaling appears during chronic administration of L-DOPA and shows a high correlation with the severity of dyskinesia. Furthermore, the abnormal activation of the D1/PKA/DARPP-32 cascade is paralleled by increased phosphorylation of the GluA1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor at the PKA Ser845 site. The GluA1 promotes excitatory AMPA receptor-mediated transmission and may be implicated in the alterations found at the corticostriatal synapses of dyskinetic animals. In our study, we investigated the role of mTORC1 pathway activation in modulating bidirectional striatal synaptic plasticity in L-DOPA-treated parkinsonian rats. Inhibition of mTORC1 by coadministration of rapamycin to L-DOPA was able to limit the magnitude of LID expression, accounting for a therapeutic effect of this

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Section: Introductionmentioning

confidence: 99%

Rapamycin, by Inhibiting mTORC1 Signaling, Prevents the Loss of Striatal Bidirectional Synaptic Plasticity in a Rat Model of L-DOPA-Induced Dyskinesia

Calabrese

Maio

Marino

et al. 2020

Front. Aging Neurosci.

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“…As the main hallmark in PD is the lack of DAergic innervation in the striatum, drug-based treatments rely on exogenous administration of compounds with DAergic activity (i.e., levodopa, DA agonists) to replace the depleted neurotransmitter (Zahoor et al, 2018). L-dopa is currently the most effective drug for PD.…”

Section: Treatments For Pdmentioning

confidence: 99%

Is the Immunological Response a Bottleneck for Cell Therapy in Neurodegenerative Diseases?

Salado-Manzano

Perpiñá

Straccia³

et al. 2020

Front. Cell. Neurosci.

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Neurodegenerative disorders such as Parkinson's (PD) and Huntington's disease (HD) are characterized by a selective detrimental impact on neurons in a specific brain area. Currently, these diseases have no cures, although some promising trials of therapies that may be able to slow the loss of brain cells are underway. Cell therapy is distinguished by its potential to replace cells to compensate for those lost to the degenerative process and has shown a great potential to replace degenerated neurons in animal models and in clinical trials in PD and HD patients. Fetal-derived neural progenitor cells, embryonic stem cells or induced pluripotent stem cells are the main cell sources that have been tested in cell therapy approaches. Furthermore, new strategies are emerging, such as the use of adult stem cells, encapsulated cell lines releasing trophic factors or cell-free products, containing an enriched secretome, which have shown beneficial preclinical outcomes. One of the major challenges for these potential new treatments is to overcome the host immune response to the transplanted cells. Immune rejection can cause significant alterations in transplanted and endogenous tissue and requires immunosuppressive drugs that may produce adverse effects. T-, B-lymphocytes and microglia have been recognized as the main effectors in striatal graft rejection. This review aims to summarize the preclinical and clinical studies of cell therapies in PD and HD. In addition, the precautions and strategies to ensure the highest quality of cell grafts, the lowest risk during transplantation and the reduction of a possible immune rejection will be outlined. Altogether, the wide-ranging possibilities of advanced therapy medicinal products (ATMPs) could make therapeutic treatment of these incurable diseases possible in the near future.

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“…This marks the end of the "honeymoon" period. After some years (4-6 years), patients begin to experience, most strikingly, its intense side effects [33,34].…”

Section: Parkinson's Disease Treatmentmentioning

confidence: 99%

“…These long-term complications included many kinds of motor fluctuations. In addition to the on-off phenomenon, already described above, the patients may also experience delay on, when medication takes a longer period to take its effect; freezing phenomenon, which was already discussed during the motor signs presentation; and dyskinesia, which is determined by the presence of hyperkinetic involuntary movements, including twitches, jerking, twisting, or simple restlessness but no tremor, occurring when the drug is at its peak dose, during the wearing-off period or even during off-periods of the medication [29,34]. Several new formulations of levodopa have been developed to provide a more stable levodopa plasma concentration, reducing some of the side effects, including dyskinesia.…”

Section: Parkinson's Disease Treatmentmentioning

confidence: 99%

Parkinson’s Disease Rehabilitation: Effectiveness Approaches and New Perspectives

Vasconcelos¹

2020

Physical Therapy Effectiveness

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Parkinson's disease has been considered one of the most important and common neurodegenerative diseases in the world. Its motor and nonmotor signs determine a huge functional loss, leading the individuals to lose their independence. Although the treatment requires a pharmacological approach, physical therapy has confirmed its importance in this process. Today, neurorehabilitation is indispensable to increase many of the cardinal signs of the disease. Using traditional or technological approaches, physical therapy has reached good results in improving motor and nonmotor functions, as well as the quality of life of Parkinsonians. However, it is important to develop and to fortify the physical therapy approach so that we can provide stronger evidence about our practice.

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Pharmacological Treatment of Parkinson’s Disease

Cited by 73 publications

References 60 publications

Rapamycin, by Inhibiting mTORC1 Signaling, Prevents the Loss of Striatal Bidirectional Synaptic Plasticity in a Rat Model of L-DOPA-Induced Dyskinesia

Rapamycin, by Inhibiting mTORC1 Signaling, Prevents the Loss of Striatal Bidirectional Synaptic Plasticity in a Rat Model of L-DOPA-Induced Dyskinesia

Is the Immunological Response a Bottleneck for Cell Therapy in Neurodegenerative Diseases?

Parkinson’s Disease Rehabilitation: Effectiveness Approaches and New Perspectives

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