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Journal of Neural Transmission (Vienna,... Sep 2022The question whether life style may impair the advent or course of the disease in patients with Parkinsonism is of great importance for patients and physicians alike. We... (Review)
Review
The question whether life style may impair the advent or course of the disease in patients with Parkinsonism is of great importance for patients and physicians alike. We present here comprehensive information on the influence of the environment, diet (especially caffeine, nicotine, alcohol, chocolate and dairy products), physical activity and sleep on risk and course of Parkinson's disease.
Topics: Caffeine; Exercise; Humans; Life Style; Parkinson Disease; Parkinsonian Disorders
PubMed: 35606622
DOI: 10.1007/s00702-022-02509-1 -
Continuum (Minneapolis, Minn.) Oct 2022The differential diagnosis of parkinsonism (tremor, rigidity, bradykinesia, and gait difficulty/postural instability) is broad and includes two neurodegenerative... (Review)
Review
PURPOSE OF REVIEW
The differential diagnosis of parkinsonism (tremor, rigidity, bradykinesia, and gait difficulty/postural instability) is broad and includes two neurodegenerative conditions that exist on a clinicopathologic spectrum: progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Early in their clinical course, PSP and CBS may be difficult to distinguish from Parkinson disease and several other illnesses, but it is crucial to do so because of implications for management and prognosis.
RECENT FINDINGS
Early accurate diagnosis of PSP and CBS remains a challenge because of heterogeneity in presenting symptoms and high frequency of coexisting pathologies (especially Alzheimer disease and vascular disease). It is increasingly recognized that patients with PSP, CBS, and other parkinsonian disorders require multidisciplinary care for optimal outcomes. With the recent proliferation of biomarker studies and therapeutic trials for tauopathies, there is growing hope that better treatments for PSP and CBS are on the horizon.
SUMMARY
Although PSP and CBS currently lack disease-modifying therapies, it is important to diagnose them as early as possible so that the patient can benefit from the many available symptomatic therapies, support groups, and a growing number of clinical trials.
Topics: Biomarkers; Corticobasal Degeneration; Humans; Parkinson Disease; Parkinsonian Disorders; Supranuclear Palsy, Progressive
PubMed: 36222770
DOI: 10.1212/CON.0000000000001158 -
Journal of Parkinson's Disease 2017The identification of MPTP, a relatively simple compound which causes selective degeneration of the substantia nigra after systemic administration, has had an a... (Review)
Review
The identification of MPTP, a relatively simple compound which causes selective degeneration of the substantia nigra after systemic administration, has had an a significant impact on the understanding and treatment of Parkinson’s disease (PD) over the last 30 years. This article is prefaced by the intriguing “medical detective story” that lead to the discovery of the biological effects of MPTP in humans. The steps that lead to the unraveling its mechanism of action and their impact on research into pathways underlying nigrostriatal degeneration are reviewed. The impact of the animal models that have been developed utilizing MPTP is also described with a focus on the translational implications of MPTP-related research. These include use of MAO-B inhibitors aimed at neuroprotection in PD and the importance of a stable primate model for PD which was utilized to better understand the circuitry of the basal ganglia, and the identification of the subthalamic nucleus as a target for deep brain stimulation. Finally, the results of a broad range of epidemiologic studies aimed as assessing the impact of environmental factors in PD that have been inspired by MPTP are summarized, including the discovery of other neurotoxicants (rotenone and paraquat) with parkinsonogenic effects. Overall, this article attempts to describe how the discovery of this nigral neurotoxicant began, where it is currently, and what the future may hold.
Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Corpus Striatum; Disease Models, Animal; History, 20th Century; Humans; Parkinson Disease; Parkinsonian Disorders; Substantia Nigra; Translational Research, Biomedical
PubMed: 28282815
DOI: 10.3233/JPD-179006 -
Journal of Medical Genetics Feb 2018Parkinson's disease (PD) is a complex and heterogeneous neurological condition characterised mainly by bradykinesia, resting tremor, rigidity and postural instability,... (Review)
Review
Parkinson's disease (PD) is a complex and heterogeneous neurological condition characterised mainly by bradykinesia, resting tremor, rigidity and postural instability, symptoms that together comprise the parkinsonian syndrome. Non-motor symptoms preceding and following clinical onset are also helpful diagnostic markers revealing a widespread and progressive pathology. Many other neurological conditions also include parkinsonism as primary or secondary symptom, confounding their diagnosis and treatment. Although overall disease course and end-stage pathological examination single out these conditions, the significant overlaps suggest that they are part of a continuous disease spectrum. Recent genetic discoveries support this idea because mutations in a few genes (α-synuclein, , tau) can cause partially overlapping pathologies. Additionally, mutations in causative genes and environmental toxins identify protein homeostasis and the mitochondria as key mediators of degeneration of dopaminergic circuits in the basal ganglia. The evolving mechanistic insight into the pathophysiology of PD and related conditions will contribute to the development of targeted and effective symptomatic treatments into disease-modifying therapies that will reduce the burden of these dreadful conditions.
Topics: Dopamine; Genes, Dominant; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Mitochondria; Mutation; Neurons; Parkinson Disease; Parkinsonian Disorders; alpha-Synuclein; tau Proteins
PubMed: 29151060
DOI: 10.1136/jmedgenet-2017-105047 -
Tidsskrift For Den Norske Laegeforening... Feb 2017
Topics: Humans; Parkinson Disease; Parkinsonian Disorders; Terminology as Topic
PubMed: 28225240
DOI: 10.4045/tidsskr.16.0915 -
Current Neurology and Neuroscience... Sep 2017This article reviews was to review genes where putative or confirmed pathogenic mutations causing Parkinson's disease or Parkinsonism have been identified since 2012,... (Review)
Review
PURPOSE OF REVIEW
This article reviews was to review genes where putative or confirmed pathogenic mutations causing Parkinson's disease or Parkinsonism have been identified since 2012, and summarizes the clinical and pathological picture of the associated disease subtypes.
RECENT FINDINGS
Newly reported genes for dominant Parkinson's disease are DNAJC13, CHCHD2, and TMEM230. However, the evidence for a disease-causing role is not conclusive, and further genetic and functional studies are warranted. RIC3 mutations have been reported from one family but not yet encountered in other patients. New genes for autosomal recessive disease include SYNJ1, DNAJC6, VPS13C, and PTRHD1. Deletions of a region on chromosome 22 (22q11.2del) are also associated with early-onset PD, but the mode of inheritance and the underlying causative gene remain unclear. PODXL mutations were reported in autosomal recessive PD, but their roles remain to be confirmed. Mutations in RAB39B cause an X-linked Parkinsonian disorder. Mutations in the new dominant PD genes have generally been found in medium- to late-onset Parkinson's disease. Many mutations in the new recessive and X-chromosomal genes cause severe atypical juvenile Parkinsonism, but less devastating mutations in these genes may cause PD.
Topics: DNA-Binding Proteins; Genetic Association Studies; Humans; Intracellular Signaling Peptides and Proteins; Mitochondrial Proteins; Mutation; Parkinson Disease; Parkinsonian Disorders; Transcription Factors; Ubiquitin-Protein Ligases
PubMed: 28733970
DOI: 10.1007/s11910-017-0780-8 -
Annual Review of Biochemistry Jun 2023The polyamines putrescine, spermidine, and spermine are abundant polycations of vital importance in mammalian cells. Their cellular levels are tightly regulated by... (Review)
Review
The polyamines putrescine, spermidine, and spermine are abundant polycations of vital importance in mammalian cells. Their cellular levels are tightly regulated by degradation and synthesis, as well as by uptake and export. Here, we discuss the delicate balance between the neuroprotective and neurotoxic effects of polyamines in the context of Parkinson's disease (PD). Polyamine levels decline with aging and are altered in patients with PD, whereas recent mechanistic studies on ATP13A2 (PARK9) demonstrated a driving role of a disturbed polyamine homeostasis in PD. Polyamines affect pathways in PD pathogenesis, such as α-synuclein aggregation, and influence PD-related processes like autophagy, heavy metal toxicity, oxidative stress, neuroinflammation, and lysosomal/mitochondrial dysfunction. We formulate outstanding research questions regarding the role of polyamines in PD, their potential as PD biomarkers, and possible therapeutic strategies for PD targeting polyamine homeostasis.
Topics: Animals; Humans; Parkinson Disease; Polyamines; Neuroprotection; Parkinsonian Disorders; Spermidine; Mammals
PubMed: 37018845
DOI: 10.1146/annurev-biochem-071322-021330 -
Current Opinion in Neurology Aug 2023Our knowledge of the genetic architecture underlying Parkinson's disease has vastly improved in the past quarter century. About 5-10% of all patients suffer from a... (Review)
Review
PURPOSE OF REVIEW
Our knowledge of the genetic architecture underlying Parkinson's disease has vastly improved in the past quarter century. About 5-10% of all patients suffer from a monogenic form of Parkinson's disease.
RECENT FINDINGS
Mutations in autosomal dominant genes (e.g. SNCA, LRRK2, VPS35) or autosomal recessive genes (e.g. PRKN, PINK1, DJ-1) can cause genetic Parkinson's disease. Recessive DNAJC6 mutations can present predominantly as atypical parkinsonism, but also rarely as typical Parkinson's disease. Majority of Parkinson's disease is genetically complex. Mutation in RIC3 , a chaperone of neuronal nicotinic acetylcholine receptor subunit α-7 (CHRNA7), provides strong evidence for the role of cholinergic pathway, for the first time, in cause of Parkinson's disease. X-linked parkinsonism manifests at a young age accompanied by many (atypical) features such as intellectual disability, spasticity, seizures, myoclonus, dystonia, and have poor response to levodopa.
SUMMARY
This review article aims to provide a comprehensive overview on Parkinson's disease genetics. MAPT , which encodes the microtubule associated protein tau, TMEM230, LRP10, NUS1 and ARSA are the five new putative disease-causing genes in Parkinson's disease. The validation of novel genes and its association with Parkinson's disease remains extremely challenging, as genetically affected families are sparse and globally widespread. In the near future, genetic discoveries in Parkinson's disease will influence our ability to predict and prognosticate the disease, help in defining etiological subtypes that are critical in implementation of precision medicine.
Topics: Humans; Parkinson Disease; Membrane Proteins; Parkinsonian Disorders; Mutation; Seizures; LDL-Receptor Related Proteins; Receptors, Cell Surface
PubMed: 37366140
DOI: 10.1097/WCO.0000000000001167 -
Journal of Parkinson's Disease 2020In people with young onset Parkinson's disease (YOPD), onset of symptoms is between 21 and 40 years of age. The distinction between YOPD and late-onset Parkinson's... (Review)
Review
In people with young onset Parkinson's disease (YOPD), onset of symptoms is between 21 and 40 years of age. The distinction between YOPD and late-onset Parkinson's disease is supported by genetic differences (a genetic etiology is more common in people with YOPD) and clinical differences (e.g., dystonia and levodopa-induced dyskinesias are more common inYOPD). Moreover, people with YOPD tend to have different family and societal engagements compared to those with late-onset PD. These unique features have implications for clinical management, and call for a tailored multidisplinary approach involving shared-decision making.
Topics: Adult; Age of Onset; Disease Management; Dystonia; Female; Humans; Male; Parkinson Disease; Pregnancy; Pregnancy Complications; Social Interaction; Work Schedule Tolerance; Young Adult
PubMed: 32651336
DOI: 10.3233/JPD-202135 -
Journal of Integrative Neuroscience Sep 2023Continuous medical progress is significantly improving the quality of health care. As a result, people are living longer than during the past century, but this has also... (Review)
Review
Continuous medical progress is significantly improving the quality of health care. As a result, people are living longer than during the past century, but this has also caused an increase of the prevalence of many neurological disorders. Parkinson's disease (PD) is the fastest growing neurological condition, with a doubling of cases reported between 1995 and 2015 and a further doubling projected by 2030. Parkinson's disease is generally associated with characteristic motor symptoms (resting tremor, rigidity, bradykinesia and postural instability). However, patients with PD also experience many non-motor symptoms that might be at least as debilitating as the motor symptoms and which significantly impact patients' quality of life (QoL). Pain is a frequent yet underrecognized symptom; the incidence in PD is much higher than in the general population and constitutes a silent disability that significantly contributes to a deterioration in QoL. Accurate identification of parkinsonian pain is important for its diagnosis and effective treatment. In this review, we provide an overview of the pathophysiology, classification, and management of pain in PD. We define the various modalities of chronic PD pain, suggesting possible explanations for its relationship with PD pathology, and discuss its management and currently recommended therapies.
Topics: Humans; Parkinson Disease; Quality of Life; Chronic Pain
PubMed: 37735139
DOI: 10.31083/j.jin2205132