Late-stage Parkinson disease

Department of Neuroscience, Hospital Santa Maria, Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal.
Nature Reviews Neurology (Impact Factor: 15.36). 07/2012; 8(8):435-42. DOI: 10.1038/nrneurol.2012.126
Source: PubMed


The cardinal symptoms of Parkinson disease (PD) are asymmetrical bradykinesia, rigidity, resting tremor and postural instability. However, the presence and spectrum of, and disability caused by, nonmotor symptoms (NMS) are being increasingly recognized. NMS include dementia, psychosis, depression and apathy, and are a major source of disability in later stages of PD, in association with axial symptoms that are resistant to levodopa therapy. The model of clinical progression of PD should, therefore, incorporate NMS, instead of being restricted to motor signs and levodopa-induced motor complications. Patients with disabling motor complications are classified as having advanced PD, which has been thought to represent the ultimate stage of disease. However, deep brain stimulation to treat motor complications has dramatically changed this scenario, with implications for the definition of advanced-stage disease. As treatment improves and survival times increase, patients are increasingly progressing to a later phase of disease in which they are highly dependent on caregivers, and disability is dominated by motor symptoms and NMS that are resistant to levodopa. In this article, we review the changing landscape of the later stages of PD, and propose a definition of late-stage PD to designate patients who have progressed beyond the advanced stage.

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    • "Alzheimer ' s ( AD ) and Parkinson ' s disease ( PD ) are the most prevalent and highly characterized neurodegenerative disorders ( Ballard et al . 2011 ; Coelho and Ferreira 2012 ) . AD is characterized by the abnormal deposition of the Tau protein , with increased pro - duction and impaired clearance of the beta amyloid peptides generated from neurons ( O ' Brien and Wong 2011 ) . "
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    Cell and Tissue Research 02/2014; 358(1). DOI:10.1007/s00441-013-1787-3 · 3.57 Impact Factor
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    • "The apparent symptoms of PD are movement disorders, including muscle rigidity, bradykinesia, and tremors. Nevertheless, behavioral and cognitive problems, including dementia, depression, anxiety, and sleep disturbances, are also involved in the later stages of the disease [1]. Two clinical-pathological findings describe both familial and sporadic PD: the development of Lewy bodies (aggregation of α-synuclein) in the brain tissue and the selective loss of midbrain dopaminergic (DA) neurons in the substantia nigra [2]. "
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    ABSTRACT: Parkinson's disease (PD) is the second most common degenerative disorder of the central nervous system that impairs motor skills and cognitive function. To date, the disease has no effective therapies. The identification of new drugs that provide benefit in arresting the decline seen in PD patients is the focus of much recent study. However, the lengthy time frame for the progression of neurodegeneration in PD increases both the time and cost of examining potential therapeutic compounds in mammalian models. An alternative is to first evaluate the efficacy of compounds in Caenorhabditis elegans models, which reduces examination time from months to days. n-Butylidenephthalide is the naturally-occurring component derived from the chloroform extract of Angelica sinensis. It has been shown to have anti-tumor and anti-inflammatory properties, but no reports have yet described the effects of n-butylidenephthalide on PD. The aim of this study was to assess the potential for n-butylidenephthalide to improve PD in C. elegans models. In the current study, we employed a pharmacological strain that expresses green fluorescent protein specifically in dopaminergic neurons (BZ555) and a transgenic strain that expresses human α-synuclein in muscle cells (OW13) to investigate the antiparkinsonian activities of n-butylidenephthalide. Our results demonstrate that in PD animal models, n-butylidenephthalide significantly attenuates dopaminergic neuron degeneration induced by 6-hydroxydopamine; reduces α-synuclein accumulation; recovers lipid content, food-sensing behavior, and dopamine levels; and prolongs life-span of 6-hydroxydopamine treatment, thus revealing its potential as a possible antiparkinsonian drug. n-Butylidenephthalide may exert its effects by blocking egl-1 expression to inhibit apoptosis pathways and by raising rpn-6 expression to enhance the activity of proteasomes. n-Butylidenephthalide may be one of the effective neuroprotective agents for PD.
    PLoS ONE 01/2014; 9(1):e85305. DOI:10.1371/journal.pone.0085305 · 3.23 Impact Factor
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    • "Parkinson’s disease (PD) is a common movement disorder characterized by a progressive degeneration of dopaminergic (DA) neurons in the substantia nigra (SNc) [1]–[3]. Different genetic and environmental factors contribute to disease etiology. "
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    PLoS ONE 12/2013; 8(12):e83714. DOI:10.1371/journal.pone.0083714 · 3.23 Impact Factor
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