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Brain Sciences
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Frontiers in Parkinson’s Disease (PD)
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Frontiers in Parkinson’s Disease (PD)

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Molecular and Cellular Neuroscience".

Deadline for manuscript submissions: closed (10 November 2019) | Viewed by 38601

Special Issue Editor

Dr. Alicia M. Pickrell

E-Mail Website
Guest Editor
School of Neuroscience, Virginia Polytechnic and State University, Blacksburg, VA 24061, USA
Interests: mitochondria; mitochondrial DNA; mitophagy; Parkinson’s disease; neurodegenerative diseases

Special Issue Information

Dear Colleagues,

Parkinson’s Disease (PD) is the most common motor deteriorating neurodegenerative disease with a majority of cases being sporadic in nature.  Over the past decade, researchers have begun to understand the physiological roles of different proteins that are mutated in monogenic forms of PD.  These insights provide information into what types of biological processes may go awry in sporadic PD and aid in our understanding of the pathophysiological changes occuring during degenerative processes. The effort of multiple research groups elucidated the mechanism by which PINK1 and Parkin (two genes mutated in recessive PD) target damaged mitochondria for autophagic removal. Recently, the substrates and phorphosylation sites for leucine-rich repeat kinase 2 (LRRK2) have been identified. LRRK2 is the gene most commonly mutated in autosomal dominant forms of PD.

Newly published large-scale genome wide association studies (GWAS) have identified risk loci and candidate genes that are also involved in PD.  It is imperitive that research efforts identify the function of these newly identified canidate genes (if unknown) and how these genes possibly contribute to neurodegeneration. The aim of this Special Issue, “Frontiers in Parkinson’s Disease,” is to encourage the publication of new experimental, translational and clinical findings to advance our understanding of the pathophysiological changes that occur in Parkinson’s Disease.

Assist. Prof. Alicia M. Pickrell
Guest Editor

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Keywords

  • Parkinson’s disease
  • Dopaminergic neurons
  • Neurodegeneration
  • Substantia nigra

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Published Papers (6 papers)

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Research

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12 pages, 1586 KiB  
Article
Beneficial Effect of Foot Plantar Stimulation in Gait Parameters in Individuals with Parkinson’s Disease
by Lorenzo Brognara, Emmanuel Navarro-Flores, Lorenzo Iachemet, Nuria Serra-Catalá and Omar Cauli
Brain Sci. 2020, 10(2), 69; https://doi.org/10.3390/brainsci10020069 - 27 Jan 2020
Cited by 26 | Viewed by 5819
Abstract
New treatments based on peripheral stimulation of the sensory-motor system have shown to be promising in rehabilitation strategies for patients with neurological disorders, including Parkinson’s disease (PD), especially in regards to reducing gait impairment, and hence, the incidence of falls. The aim of [...] Read more.
New treatments based on peripheral stimulation of the sensory-motor system have shown to be promising in rehabilitation strategies for patients with neurological disorders, including Parkinson’s disease (PD), especially in regards to reducing gait impairment, and hence, the incidence of falls. The aim of this study was to evaluate the change in several gait parameters measured by sensor inertial measurement in PD patients after acute plantar stimulation, under the distal phalanx of the big toe, and underneath the head of the first metatarsal joint of both feet, using a 3D printing insole. In order to assess whether the effects are selective for PD patients, we compared the effect of the treatment in a control group (age-matched) consisting of patients with other neurological disorders which also displayed gait and balance impairment, and a similar cognitive function, depressive symptoms, body mass index, and comorbidity burden observed in the PD group. Plantar foot stimulation in PD patients eliminated the significant (p < 0.05) alterations existing in stride asymmetry and in stride variability. When comparing the effects of post-plantar stimulation with the respective basal level, considered as 100% in both groups, we observed a significant (p = 0.019, Mann–Whitney test) increase in stride length compared to basal in the PD group and control group. No significant effects of foot plantar stimulation were observed in any of the gait parameters in the control group. Plantar foot stimulation has a positive effect on the step and stride length, and has a positive effect on walking stability, measured by the increase in stride length. No significant effect was observed on bradykinesia because it did not improve walking velocity. These findings indicate that foot plantar stimulation using a 3D printing insole seems to generate a more stable walking pattern in PD patients, with an interesting applicability, and a low-cost, for reducing gait impairment in PD patients. Full article
(This article belongs to the Special Issue Frontiers in Parkinson’s Disease (PD))
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13 pages, 2774 KiB  
Article
Neuroprotective and Antioxidant Effect of Naringenin-Loaded Nanoparticles for Nose-to-Brain Delivery
by Shadab Md, Nabil A. Alhakamy, Hibah M. Aldawsari and Hani Zakaria Asfour
Brain Sci. 2019, 9(10), 275; https://doi.org/10.3390/brainsci9100275 - 15 Oct 2019
Cited by 51 | Viewed by 4465
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder resulting in a decreased nigrostriatal availability of dopamine. Oxidative stress is one factor contributing to PD. Naringenin (NAR), a flavonoid, is a potent antioxidant shown to be beneficial in experimental PD. The clinical development of NAR [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative disorder resulting in a decreased nigrostriatal availability of dopamine. Oxidative stress is one factor contributing to PD. Naringenin (NAR), a flavonoid, is a potent antioxidant shown to be beneficial in experimental PD. The clinical development of NAR has been hampered due to its low bioavailability resulting from gastrointestinal degradation, inefficient permeability, and low aqueous solubility. The objective of the present research was to formulate and characterize naringenin-loaded chitosan nanoparticles (NAR NPs) for nose-to-brain delivery. The cellular uptake, cytotoxicity, and neuroprotective effects of NAR NPs were determined using the SH-SY5Y cell line in vitro. NAR NPs were prepared using the ionic gelation method and characterized by zetasizer, transmission electron microscopy (TEM), and field emission microscopy (FESEM). The average particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, and 24 h in vitro release profile were 87.6 ± 8.47 nm, 0.31 ± 0.04, 15.36 ± 2.05 mV, 91.12 ± 2.99%, and 54.80 ± 4.22%, respectively. The percentage NAR permeation through nasal mucosa from NPs was found to be 67.90 ± 0.72%. Cellular uptake of prepared NPs was confirmed by fluorescence microscopy. Neuroprotective activity of NAR NPs was evaluated through viability assays and by estimating reactive oxygen species (ROS) levels. NAR NPs showed enhanced neuroprotective ability and antioxidant effect against 6-OHDA-induced neurotoxicity in SH-SY5Y cells. However, animal studies are necessary to establish the potential of NAR NPs to be an effective carrier for the treatment of PD for nose-to-brain delivery. Full article
(This article belongs to the Special Issue Frontiers in Parkinson’s Disease (PD))
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Review

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17 pages, 290 KiB  
Review
A Spanish Consensus on the Use of Safinamide for Parkinson’s Disease in Clinical Practice
by Javier Pagonabarraga, José Matías Arbelo, Francisco Grandas, Maria-Rosario Luquin, Pablo Martínez Martín, Mari Cruz Rodríguez-Oroz, Francesc Valldeoriola and Jaime Kulisevsky
Brain Sci. 2020, 10(3), 176; https://doi.org/10.3390/brainsci10030176 - 18 Mar 2020
Cited by 7 | Viewed by 3841
Abstract
Safinamide is an approved drug for the treatment of motor fluctuations in Parkinson’s disease (PD). Scarce data are available on its use in clinical practice. A group of Spanish movement disorders specialists was convened to review the use of safinamide across different clinical [...] Read more.
Safinamide is an approved drug for the treatment of motor fluctuations in Parkinson’s disease (PD). Scarce data are available on its use in clinical practice. A group of Spanish movement disorders specialists was convened to review the use of safinamide across different clinical scenarios that may guide neurologists in clinical practice. Eight specialists with recognized expertise in PD management elaborated the statements based on available evidence in the literature and on their clinical experience. The RAND/UCLA method was carried, with final conclusions accepted after a 2-round modified Delphi process. Higher level of agreement between panellists was reached for the following statements. Safinamide significantly improves mean daily OFF time without troublesome dyskinesias. Adjunctive treatment with safinamide is associated with motor improvements in patients with mid-to-late PD. The efficacy of safinamide on motor fluctuations is maintained at long-term, with no increase over time in dyskinesias severity. The clinical benefits of safinamide on pain and depression remain unclear. Safinamide presents a similar incidence of adverse events compared with placebo. The efficacy and safety of safinamide shown in the pivotal clinical trials are reproduced in clinical practice, with improvement of parkinsonian symptoms, decrease of daily OFF time, control of dyskinesias at the long term, and good tolerability and safety. Full article
(This article belongs to the Special Issue Frontiers in Parkinson’s Disease (PD))
16 pages, 452 KiB  
Review
Postural Instability in Parkinson’s Disease: A Review
by Bhavana Palakurthi and Sindhu Preetham Burugupally
Brain Sci. 2019, 9(9), 239; https://doi.org/10.3390/brainsci9090239 - 18 Sep 2019
Cited by 68 | Viewed by 10344
Abstract
Parkinson’s disease (PD) is a heterogeneous progressive neurodegenerative disorder, which typically affects older adults; it is predicted that by 2030 about 3% of the world population above 65 years of age is likely to be affected. At present, the diagnosis of PD is [...] Read more.
Parkinson’s disease (PD) is a heterogeneous progressive neurodegenerative disorder, which typically affects older adults; it is predicted that by 2030 about 3% of the world population above 65 years of age is likely to be affected. At present, the diagnosis of PD is clinical, subjective, nonspecific, and often inadequate. There is a need to quantify the PD factors for an objective disease assessment. Among the various factors, postural instability (PI) is unresponsive to the existing treatment strategies resulting in morbidity. In this work, we review the physiology and pathophysiology of postural balance that is essential to treat PI among PD patients. Specifically, we discuss some of the reported factors for an early PI diagnosis, including age, nervous system lesions, genetic mutations, abnormal proprioception, impaired reflexes, and altered biomechanics. Though the contributing factors to PI have been identified, how their quantification to grade PI severity in a patient can help in treatment is not fully understood. By contextualizing the contributing factors, we aim to assist the future research efforts that underpin posturographical and histopathological studies to measure PI in PD. Once the pathology of PI is established, effective diagnostic tools and treatment strategies could be developed to curtail patient falls. Full article
(This article belongs to the Special Issue Frontiers in Parkinson’s Disease (PD))
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15 pages, 1591 KiB  
Review
Found in Translation: The Utility of C. elegans Alpha-Synuclein Models of Parkinson’s Disease
by Anthony L. Gaeta, Kim A. Caldwell and Guy A. Caldwell
Brain Sci. 2019, 9(4), 73; https://doi.org/10.3390/brainsci9040073 - 28 Mar 2019
Cited by 44 | Viewed by 10419
Abstract
Parkinson’s Disease (PD) is the second-most common neurodegenerative disease in the world, yet the fundamental and underlying causes of the disease are largely unknown, and treatments remain sparse and impotent. Several biological systems have been employed to model the disease but the nematode [...] Read more.
Parkinson’s Disease (PD) is the second-most common neurodegenerative disease in the world, yet the fundamental and underlying causes of the disease are largely unknown, and treatments remain sparse and impotent. Several biological systems have been employed to model the disease but the nematode roundworm Caenorhabditis elegans (C. elegans) shows unique promise among these to disinter the elusive factors that may prevent, halt, and/or reverse PD phenotypes. Some of the most salient of these C. elegans models of PD are those that position the misfolding-prone protein alpha-synuclein (α-syn), a hallmark pathological component of PD, as the primary target for scientific interrogation. By transgenic expression of human α-syn in different tissues, including dopamine neurons and muscle cells, the primary cellular phenotypes of PD in humans have been recapitulated in these C. elegans models and have already uncovered multifarious genetic factors and chemical compounds that attenuate dopaminergic neurodegeneration. This review describes the paramount discoveries obtained through the application of different α-syn models of PD in C. elegans and highlights their established utility and respective promise to successfully uncover new conserved genetic modifiers, functional mechanisms, therapeutic targets and molecular leads for PD with the potential to translate to humans. Full article
(This article belongs to the Special Issue Frontiers in Parkinson’s Disease (PD))
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Other

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2 pages, 175 KiB  
Erratum
Erratum: Pagonabarraga, J.; et al. A Spanish Consensus on the Use of Safinamide for Parkinson’s Disease in Clinical Practice. Brain Sci. 2020, 10, 176
by Javier Pagonabarraga, José Matías Arbelo, Francisco Grandas, Maria-Rosario Luquin, Pablo Martínez Martín, Maria Cruz Rodriguez-Oroz, Francesc Valldeoriola and Jaime Kulisevsky
Brain Sci. 2020, 10(5), 313; https://doi.org/10.3390/brainsci10050313 - 22 May 2020
Cited by 2 | Viewed by 2426
Abstract
We would like to submit the following erratum to our recently published paper [...] Full article
(This article belongs to the Special Issue Frontiers in Parkinson’s Disease (PD))
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