The diagnosis and treatment of Parkinson's disease (PD) typically occur when the disease has already progressed to a relatively advanced stage in which motor symptoms are clearly evident and substantial neurophysiological damage has already taken place. Nonmotor symptoms, which account for a large proportion of PD symptoms, usually emerge much earlier and offer both an early indication for treatment and a therapeutic target. A growing body of data from the medical literature points to several critical advantages that may be associated with early therapeutic intervention in PD. The most evident benefit of early intervention is a reduction in symptoms, particularly dyskinesia, and the delay of levodopa initiation. Clinical trials suggest but have yet to conclusively demonstrate that early treatment can slow disease progression. Both the diminishment of symptoms and the potential for slowing disease progression have large implications for improving patient quality of life. The enormous direct costs associated with PD would also likely be reduced over the long term with earlier treatment. The great majority of costs attributable to PD occur when the disease is at its most advanced stage and when symptoms are most severe. An early-treatment strategy that diminishes symptoms and that has the potential to slow disease progression could have a meaningful impact on PD expenditures. Adherence, too, must be taken into consideration, particularly since PD patients are generally poorly adherent to prescribed therapies, especially therapies with complex dosing schedules. Taking advantage of more convenient and adherencefriendly drug formulations may further help to improve outcomes and lower costs in PD.
[Show abstract][Hide abstract] ABSTRACT: The localization of yellow fluorescent protein (YFP)-tagged HSP70 proteins was employed to identify stress-sensitive sites in human neurons following temperature elevation. Stable lines of human SH-SY5Y neuronal cells were established that expressed YFP-tagged protein products of the human inducible HSP70 genes HSPA6 (HSP70B') and HSPA1A (HSP70-1). Following a brief period of thermal stress, YFP-tagged HSPA6 and HSPA1A rapidly appeared at centrioles in the cytoplasm of human neuronal cells, with HSPA6 demonstrating a more prolonged signal compared to HSPA1A. Each centriole is composed of a distal end and a proximal end, the latter linking the centriole doublet. The YFP-tagged HSP70 proteins targeted the proximal end of centrioles (identified by γ-tubulin marker) rather than the distal end (centrin marker). Centrioles play key roles in cellular polarity and migration during neuronal differentiation. The proximal end of the centriole, which is involved in centriole stabilization, may be stress-sensitive in post-mitotic, differentiating human neurons.
[Show abstract][Hide abstract] ABSTRACT: Purpose
The influence of mental illness early in life on the subsequent risk of Parkinson's disease (PD) and its clinical picture remain obscure. This study investigated the effects of psychiatric diseases on a subsequent PD diagnosis.
We used the Longitudinal Health Insurance Database 2000 of Taiwan to identify 73 597 patients who visited ambulatory care centers or were hospitalized with a first-time diagnosis of anxiety, affective disorders, or schizophrenia between 2001 and 2003 as the study cohort. We also randomly selected 220 791 enrollees matched with the study cohort for comparison. Each patient was individually tracked for 6 years to identify a subsequent PD diagnosis. Stratified Cox proportional hazard regressions were performed for the analysis.
The incidence rate of PD per 1000 person-years was 4.91 (95% confidence interval [CI)] 4.71–5.12) and 1.63 (95% CI: 1.56–1.70) for the psychiatric and comparison groups, respectively. Patients with psychiatric illnesses were more vulnerable to developing PD than nonpsychiatric individuals, exhibiting a 2.38-fold increased risk (95% CI: 2.23–2.53) after other covariates were considered. Furthermore, patients with schizophrenia exhibited the highest risk for developing PD.
We suggest effective monitoring of patients with psychiatric disturbances for potential long-term neurodegenerative diseases.
Annals of epidemiology 11/2013; 24(3). DOI:10.1016/j.annepidem.2013.12.010 · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: L-DOPA reduces symptoms of Parkinson's disease (PD), but suffers from serious side effects on long-term use. Melatonin (10-30 mg/kg, 6 doses at 10 h intervals) was investigated to potentiate L-DOPA therapeutic effects in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice. Striatal tyrosine hydroxylase (TH) immunoreactivity, TH and phosphorylated ser 40 TH (p-TH) protein levels were assayed on 7th day. Nigral TH positive neurons stereology was conducted on serial sections 2.8 mm from Bregma rostrally to 3.74 mm caudally. MPTP caused 39% and 58% decrease respectively in striatal fibers and TH protein levels, but 2.5 fold increase in p-TH levels. About 35% TH neurons were lost between 360 - 600 μm from 940 μm of the entire nigra analyzed, but no neurons were lost 250 μm rostrally and 220 μm caudally. When L-DOPA in small doses (5-8 mg/kg) failed to affect MPTP-induced akinesia or catalepsy, co-administration of melatonin with L-DOPA attenuated these behaviors. Melatonin administration significantly attenuated MPTP-induced loss in striatal TH fibers (82%), TH (62%) and p-TH protein (100%) levels and nigral neurons (87-100%). Melatonin failed to attenuate MPTP-induced striatal dopamine depletion. L-DOPA administration (5 mg/kg, once 40 min prior to sacrifice, p.o.) in MPTP and melatonin treated mice caused significant increase in striatal dopamine (31%), as compared to L-DOPA and MPTP treated mice. This was equivalent to 8 mg/kg L-DOPA administration in parkinsonian mouse. Therefore prolonged, effective use of L-DOPA in PD with lesser side effects could be achieved by treating with 60% lower doses of L-DOPA along with melatonin.
Journal of Pineal Research 04/2015; DOI:10.1111/jpi.12212 · 9.60 Impact Factor
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