Impact of Safinamide on Patient-Reported Outcomes in Parkinson's Disease.

Introduction: Parkinson's disease (PD) is a chronic and progressive neurodegenerative condition due to the degeneration of nigral dopaminergic cells. Both motor and non-motor symptoms (NMS) of PD produce a marked impairment in PD patients' quality of life (QoL), but contrary to motor features, NMS do not improve with dopamine replacement. Novel therapeutic interventions for PD have successfully controlled most motor manifestations of PD, but the management of NMS is still challenging.

Stabilization of 14-3-3 protein-protein interactions with Fusicoccin-A decreases alpha-synuclein dependent cell-autonomous death in neuronal and mouse models.

Synucleinopathies are a group of neurodegenerative diseases without effective treatment characterized by the abnormal aggregation of alpha-synuclein (aSyn) protein. Changes in levels or in the amino acid sequence of aSyn (by duplication/triplication of the aSyn gene or point mutations in the encoding region) cause familial cases of synucleinopathies. However, the specific molecular mechanisms of aSyn-dependent toxicity remain unclear.

JNK3 Overexpression in the Entorhinal Cortex Impacts on the Hippocampus and Induces Cognitive Deficiencies and Tau Misfolding.

c-Jun N-terminal kinases (JNKs) are a family of protein kinases activated by a myriad of stimuli consequently modulating a vast range of biological processes. In human postmortem brain samples affected with Alzheimer's disease (AD), JNK overactivation has been described; however, its role in AD onset and progression is still under debate. One of the earliest affected areas in the pathology is the entorhinal cortex (EC).

JNK Activation in Alzheimer's Disease Is Driven by Amyloid β and Is Associated with Tau Pathology.

c-Jun N-terminal kinase 3 (JNK3) is suggested to play a key role in neurodegenerative disorders, especially in Alzheimer's disease (AD). However, it remains unclear whether JNK or amyloid β (Aβ) appears first in the disease onset. Postmortem brain tissues from four dementia subtypes of patients (frontotemporal dementia, Lewy body dementia, vascular dementia, and AD) were used to measure activated JNK (pJNK) and Aβ levels.

Encapsulation of MSCs and GDNF in an Injectable Nanoreinforced Supramolecular Hydrogel for Brain Tissue Engineering.

The co-administration of glial cell line-derived neurotrophic factor (GDNF) and mesenchymal stem cells (MSCs) in hydrogels (HGs) has emerged as a powerful strategy to enhance the efficient integration of transplanted cells in Parkinson's disease (PD). This strategy could be improved by controlling the cellular microenvironment and biomolecule release and better mimicking the complex properties of the brain tissue. Here, we develop and characterize a drug delivery system for brain repair where MSCs and GDNF are included in a nanoparticle-modified supramolecular guest-host HA HG.

Hydrogels for brain repair: application to Parkinson's disease.

Introduction: Parkinson's disease is the second most common neurodegenerative disease. Currently, there are no curative therapies, with only symptomatic treatment available. One of the principal reasons for the lack of treatments is the problem of delivering drugs to the brain, mainly due to the blood-brain barrier.

A holistic approach to evaluating Parkinson's disease, using the Delphi method: a linear evaluation index.

Background: Parkinson's disease (PD) is a chronic disease that presents a multitude of symptoms, with symptoms of both motor and nonmotor nature. The Delphi method is widely used to create consensuses among experts in a field of knowledge.

Objective: In order to reach a consensus on the values that should be assigned to the different motor and nonmotor manifestations of Parkinson's disease, a linear evaluation index (LEI) was created.

Present and Future of Parkinson's Disease in Spain: PARKINSON-2030 Delphi Project.

Parkinson's disease (PD) is a chronic progressive and irreversible disease and the second most common neurodegenerative disease worldwide. In Spain, it affects around 120.000-150.

Mixed pathologies in pancreatic β cells from subjects with neurodegenerative diseases and their interaction with prion protein.

Protein misfolding diseases refer to a variety of disorders that develop as a consequence of the misfolding of proteins in various organs. The etiologies of Parkinson's and Alzheimer's disease remain unclear, but it seems that type two diabetes and other prediabetic states could contribute to the appearance of the sporadic forms of these diseases. In addition to amylin deposition, other amyloidogenic proteins implicated in the pathophysiology of neurodegenerative diseases could have important roles in the pathogenesis of this disease.

Blood Pressure and Risk of Cognitive Impairment: The Role of Vascular Disease in Neurodegeneration.

(1) Background: Both cerebral vascular disorders and cognitive decline increase in incidence with age. The role of cerebral vascular disease and hemodynamic changes in the development of cognitive deficits is controversial. The objective of this study was to assess the cardiovascular response during cardiac stress testing in neurologically asymptomatic individuals who developed cognitive impairment several years after previous cardiac stress testing.

Parkinson's Disease Gravity Index: A Method by means of Optimal Scaling.

Objective: This study has been designed with the aim of using optimal scaling to perform the allocation of scores and to be able to construct an indicator of the Parkinson's Disease Gravity Index. Scores were assigned to interrelated dimensions that share information about the patient's situation, to have an objective, holistic tool which integrates scores so that doctors can have a comprehensive idea of the patient's situation. 120 consecutive patients with Parkinson's diagnosis were chosen according to the United Kingdom Parkinson's Disease Society Brain Bank criteria.

Interictal amylin levels in chronic migraine patients: A case-control study.

Background: Recently, amylin and its receptors were found in different structures involved in migraine pathophysiology. Here, we evaluate interictal concentrations of amylin and calcitonin gene-related peptide in peripheral blood as biomarkers for chronic migraine.

Methods: We prospectively recruited patients with episodic migraine, chronic migraine and healthy controls.

Microglia is associated with p-Tau aggregates in the olfactory bulb of patients with neurodegenerative diseases.

The olfactory bulb (OB) seems to be the first affected structure in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Lewy body dementia (LBD). Deposits of protein aggregates, increased dopaminergic neurons, and decreased cholinergic inputs have all been described in the OB of these diseases. We investigated here the contribution of the activated microglial cells to the increased deposits of protein aggregates.

Erratum: Pagonabarraga, J.; et al. A Spanish Consensus on the Use of Safinamide for Parkinson's Disease in Clinical Practice. 2020, , 176.

We would like to submit the following erratum to our recently published paper [...

A Spanish Consensus on the Use of Safinamide for Parkinson's Disease in Clinical Practice.

Safinamide is an approved drug for the treatment of 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.

Excess abdominal fat is associated with cutaneous allodynia in individuals with migraine: a prospective cohort study.

Objective: To investigate the specific relationship between cutaneous allodynia (CA) and the percentages of body fat (BF) and abdominal fat in migraineurs. Additionally, we compared serum levels of inflammatory biomarkers in patients with and without CA.

Background: Excess abdominal fat might facilitate progressive changes in nociceptive thresholds causing central sensitization, clinically reflected as CA, which could drive migraine progression.

Amylin as a potential link between type 2 diabetes and alzheimer disease.

Objective: Alzheimer disease (AD) is the leading cause of dementia, and although its etiology remains unclear, it seems that type 2 diabetes mellitus (T2DM) and other prediabetic states of insulin resistance could contribute to the appearance of sporadic AD. As such, we have assessed whether tau and β-amyloid (Aβ) deposits might be present in pancreatic tissue of subjects with AD, and whether amylin, an amyloidogenic protein deposited in the pancreas of T2DM patients, might accumulate in the brain of AD patients.

Methods: We studied pancreatic and brain tissue from 48 individuals with no neuropathological alterations and from 87 subjects diagnosed with AD.

Cardiac sympathetic innervation in the MPTP non-human primate model of Parkinson disease.

Purpose: Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces degeneration of dopaminergic neurons and reproduces the motor features of Parkinson disease (PD); however, the effect of MPTP on extranigral structures has been poorly studied. The aim of this research was to study the cardiac sympathetic innervation of control and MPTP-treated monkeys in order to describe the influence of MPTP toxicity on cardiac tissue.

Methods: Eight monkeys were included in the study and divided into two groups, four monkeys serving as controls and four forming the MPTP group.

Small fiber neuropathy and phosphorylated alpha-synuclein in the skin of E46K-SNCA mutation carriers.

Background And Objective: In 2004 we described the E46K mutation in alpha-synuclein gene (E46K-SNCA), a rare point mutation causing an aggressive Lewy body disease with early prominent non-motor features and small fiber denervation of myocardium. Considering the potential interest of the skin as a target for the development of biomarkers in Parkinson's Disease (PD), in this work we aimed to evaluate structural and functional integrity of small autonomic nerve fibers and phosphorylated alpha-synuclein (p-synuclein) deposition in the skin of E46K-SNCA carriers as compared to those observed in parkin gene mutation (PARK2) carriers and healthy controls.

Patients And Methods: We studied 7 E46K-SNCA carriers (3 dementia with Lewy bodies, 2 pure autonomic failure, 1 PD and 1 asymptomatic), 2 PARK2 carriers and 2 healthy controls to quantify intraepidermal nerve fiber density and p-synuclein deposition with cervical skin punch biopsies (immunohistochemistry against anti PGP9.

Combining Gene Transfer and Nonhuman Primates to Better Understand and Treat Parkinson's Disease.

Parkinson's disease (PD) is a progressive CNS disorder that is primarily associated with impaired movement. PD develops over decades and is linked to the gradual loss of dopamine delivery to the striatum, the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). While the administration of L-dopa and deep brain stimulation are potent therapies, their costs, side effects and gradual loss of efficacy underlines the need to develop other approaches.

Validation of a simple screening tool for early diagnosis of advanced Parkinson's disease in daily practice: the CDEPA questionnaire.

Early clinical diagnosis of advanced Parkinson's disease (APD) may be difficult. This study aimed to validate a simple screening tool, the CDEPA questionnaire ("Cuestionario De Enfermedad de Parkinson Avanzada" [Questionnaire for Advanced Parkinson's Disease]), for the identification of APD in daily practice. The study included 173 consecutively selected patients with PD (40% were women, mean age was 68.

The expression of cannabinoid type 1 receptor and 2-arachidonoyl glycerol synthesizing/degrading enzymes is altered in basal ganglia during the active phase of levodopa-induced dyskinesia.

Management of levodopa-induced dyskinesias (LID) is one of the main challenges in the treatment of Parkinson's disease patients. Mechanisms involved in the appearance of these involuntary movements are not well known but modifications in the activity of different neurotransmitter pathways seem to play an important role. The objective of this study was to determine differences in the expression levels of the endocannabinoid system (ECS) elements that would support a role in LID.

Interaction of amyloidogenic proteins in pancreatic β cells from subjects with synucleinopathies.

Parkinson's disease patients experience a wide range of non-motor symptoms that may be provoked by deposits of phosphorylated α-synuclein in the peripheral nervous system. Pre-existing diabetes mellitus might be a risk factor for developing Parkinson's disease, and indeed, nearly 60% of Parkinson's disease patients are insulin resistant. Thus, we have investigated whether phosphorylated α-synuclein is deposited in pancreatic tissue of subjects with synucleinopathies.