Substantia nigra

Parkinson's disease (PD) is a neurodegenerative disease featured by progressive loss of nigrostriatal dopaminergic neurons, the etiology of which is associated with the existence of neuroinflammatory response and oxidative stress. Vincamine is an indole alkaloid that was reported to exhibit potent anti-inflammatory and antioxidant properties in many central and/or peripheral diseases. Nevertheless, the specific role of vincamine in PD development remains unknown. In our study, dopaminergic neuron loss was determined through immunohistochemistry staining and western blot analysis of tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of PD mice...

Glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic neurons in various models of Parkinson's disease (PD). Cell-based GDNF gene delivery mitigates neurodegeneration and improves both motor and non-motor functions in PD mice. As PD is a chronic condition, this study aims to investigate the long-lasting benefits of hematopoietic stem cell (HSC)-based macrophage/microglia-mediated CNS GDNF (MMC-GDNF) delivery in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model. The results indicate that GDNF treatment effectively ameliorated MPTP-induced motor deficits for up to 12 months, which coincided with the protection of nigral dopaminergic neurons and their striatal terminals...

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Neurodegeneration of the substantia nigra (SN) and diminished release of dopamine are prominent causes of this progressive disease. The current study aims to evaluate the protective potential of ethanolic extract of Mentha piperita (EthMP) against rotenone-mediated PD features, dopaminergic neuronal degeneration, oxidative stress and neuronal survival in a mouse model. Swiss albino male mice were assigned to five groups: control (2...

Parkinson's disease (PD) is an aging-associated neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra and the presence of Lewy bodies containing α-synuclein within these neurons. Oligomeric α-synuclein exerts neurotoxic effects through mitochondrial dysfunction, glial cell inflammatory response, lysosomal dysfunction and so on. α-synuclein aggregation, often accompanied by oxidative stress, is generally considered to be a key factor in PD pathology...

The renin-angiotensin system (RAS) was classically considered a circulating hormonal system that regulates blood pressure. However, different tissues and organs, including the brain, have a local paracrine RAS. Mutual regulation between the dopaminergic system and RAS has been observed in several tissues. Dysregulation of these interactions leads to renal and cardiovascular diseases, as well as progression of dopaminergic neuron degeneration in a major brain center of dopamine/angiotensin interaction such as the nigrostriatal system...

In order to study the neuroprotective mechanism of cinnamaldehyde on reserpine-induced Parkinson's disease(PD) rat models, 72 male Wistar rats were randomly divided into blank group, model group, Madopar group, and cinnamaldehyde high-, medium-, and low-dose groups. Except for the blank group, the other groups were intraperitoneally injected with reserpine of 0.1 mg·kg~(-1) once every other morning, and cinnamaldehyde and Madopar solutions were gavaged every afternoon. Open field test, rotarod test, and oral chewing movement evaluation were carried out in the experiment...

Dystonia is supposed to arise from abnormalities in the motor loop of the basal ganglia; however, there is an ongoing debate regarding cerebellar involvement. We adopted the established cerebellar dystonia mice model by injecting ouabain to examine the contribution of the cerebellum. Initially, we examined whether the entopeduncular nucleus (EPN), substantia nigra pars reticulata (SNr), globus pallidus externus (GPe), and striatal neurons were activated in the model. Next, we examined whether dopamine D1 receptor agonists (D1 agonist) and dopamine D2 receptor antagonists (D2 antagonist) or selective ablation of striatal parvalbumin (PV) interneurons could modulate their involuntary movements...

Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease, and it is characterized by the intracellular and extracellular accumulation of α-synuclein (α-syn) and Tau, which are major components of cytosolic protein inclusions called Lewy bodies, in the brain. Currently, there is a lack of effective methods that preventing PD progression. It has been suggested that the plasminogen activation system, which is a major extracellular proteolysis system, is involved in PD pathogenesis...

Mitochondrial dysfunction and reactive oxygen species (ROS) accumulation within the substantia nigra pars compacta (SNpc) are central drivers of dopaminergic (DA) neuron death in Parkinson's disease (PD). Guanylyl cyclases and their second messenger cyclic (c)GMP support mitochondrial function, protecting against ROS and promoting cell survival in several tissues. However, the role of the guanylyl cyclase-cGMP axis in defining the vulnerability of DA neurons in the SNpc in PD remains unclear, in part due to the challenge of manipulating cGMP levels selectively in midbrain DA neurons...

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra and other brain regions. A key pathological feature of PD is the abnormal accumulation of α-synuclein protein within affected neurons, manifesting as Lewy bodies and Lewy neurites. Despite extensive research efforts spanning several decades, the underlying mechanisms of PD and disease-modifying therapies remain elusive. This review provides an overview of current trends in basic research on PD...

The accumulation of misfolded and aggregated α-synuclein can trigger endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), leading to apoptotic cell death in patients with Parkinson's disease (PD). As the major ER chaperone, glucose-regulated protein 78 (GRP78/BiP/HSPA5) plays a key role in UPR regulation. GRP78 overexpression can modulate the UPR, block apoptosis, and promote the survival of nigral dopamine neurons in a rat model of α-synuclein pathology. Here, we explore the therapeutic potential of intranasal exogenous GRP78 for preventing or slowing PD-like neurodegeneration in a lactacystin-induced rat model...

Traumatic brain injury (TBI) is associated with an increased risk of developing Parkinson's disease (PD), though the exact mechanisms remain unclear. TBI triggers acute neuroinflammation and catecholamine dysfunction post-injury, both implicated in PD pathophysiology. The long-term impact on these pathways following TBI, however, remains uncertain. In this study, male Sprague-Dawley rats underwent sham surgery or Marmarou's impact acceleration model to induce varying TBI severities: single mild TBI (mTBI), repetitive mild TBI (rmTBI), or moderate-severe TBI (msTBI)...

BACKGROUND: MAPT is a causative gene in frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), a hereditary degenerative disease with various clinical manifestations, including progressive supranuclear palsy, corticobasal syndrome, Parkinson's disease, and frontotemporal dementia. OBJECTIVES: To analyze genetically, biochemically, and pathologically multiple members of two families who exhibited various phenotypes of the disease. METHODS: Genetic analysis included linkage analysis, homozygosity haplotyping, and exome sequencing...

Parkinson's disease is predominantly caused by dopaminergic neuron loss in the substantia nigra pars compacta and the accumulation of alpha-synuclein protein. Though the general consensus is that several factors, such as aging, environmental factors, mitochondrial dysfunction, accumulations of neurotoxic alpha-synuclein, malfunctions of the lysosomal and proteasomal protein degradation systems, oxidative stress, and neuroinflammation, are involved in the neurodegeneration process of Parkinson's disease, the precise mechanism by which all of these factors are triggered remains unknown...

INTRODUCTION: The presence of a widespread cortical synucleinopathy is the main neuropathological hallmark underlying clinical entities such as Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB). There currently is a pressing need for the development of non-human primate (NHPs) models of PDD and DLB to further overcome existing limitations in drug discovery. METHODS: Here we took advantage of a retrogradely-spreading adeno-associated viral vector serotype 9 coding for the alpha-synuclein A53T mutated gene (AAV9-SynA53T) to induce a widespread synucleinopathy of cortical and subcortical territories innervating the putamen...

The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential disease-modifying efficacy, have difficulty in crossing the blood-brain barrier (BBB) due to their large molecular weight. Herein, we fabricate multi-functionalized lipid nanoparticles (LNP) Lpc-BoSA/CSO with BBB targeting, permeability-increasing and responsive release functions. Borneol is chemically bonded with stearic acid and, as one of the components of Lpc-BoSA/CSO, is used to increase BBB permeability...

AIMS: Sleep disturbance is a prevalent nonmotor symptom of Parkinson's disease (PD), however, assessing sleep conditions is always time-consuming and labor-intensive. In this study, we performed an automatic sleep-wake state classification and early diagnosis of PD by analyzing the electrocorticography (ECoG) and electromyogram (EMG) signals of both normal and PD rats. METHODS: The study utilized ECoG power, EMG amplitude, and corticomuscular coherence values extracted from normal and PD rats to construct sleep-wake scoring models based on the support vector machine algorithm...

Parkinson disease (PD) is a neurodegenerative disorder marked by the preferential dysfunction and death of dopaminergic neurons in the substantia nigra. The onset and progression of PD is influenced by a diversity of genetic variants, many of which lack functional characterization. To identify the most high-yield targets for therapeutic intervention, it is important to consider the core cellular compartments and functional pathways upon which the varied forms of pathogenic dysfunction may converge. Here, we review several key PD-linked proteins and pathways, focusing on the mechanisms of their potential convergence in disease pathogenesis...

BACKGROUND: Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, following Alzheimer's disease. The onset of PD is characterized by the loss of dopaminergic neurons in the substantia nigra. Stem cell therapy has great potential for the treatment of neurodegenerative diseases, and human nasal turbinate-derived stem cells (hNTSCs) have been found to share some characteristics with mesenchymal stem cells. Although the Hippo signaling pathway was originally thought to regulate cell size in organs, recent studies have shown that it can also control inflammation in neural cells...

Parkinson's disease (PD) is a common neurodegenerative disease with progressive loss of dopaminergic neurons in substantia nigra and the presence of α-synuclein-immunoreactive inclusions. Gaucher's disease is caused by homozygous mutations in β-glucocerebrosidase gene (GBA). GBA mutation carriers have an increased risk of PD. Coptis chinensis (C. chinensis) rhizome extract is a major herb widely used to treat human diseases. This study examined the association of GBA L444P mutation with Taiwanese PD in 1016 cases and 539 controls...