Pathogenesis and preclinical course of Parkinson’s disease

Foley, Paul; Riederer, Peter

doi:10.1007/978-3-7091-6360-3_2

Cited by 42 publications

(16 citation statements)

References 202 publications

(160 reference statements)

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“…Changes in DTI indices can result from a number of processes including neuronal loss and gliosis, as well as disturbances in axonal membranes, myelin sheath, microtubules, and neurofilaments (Shenton et al 2012). PD has been associated with cytoskeletal damage of various neuronal cells including dopaminergic, glutamatergic, cholinergic, tryptaminergic, GABAergic, noradrenergic and adrenergic neurons (Braak et al 1994(Braak et al , 1995(Braak et al , 1998Foley and Riederer 1999;Jellinger 1991). The cytoskeletal damage leads to Lewy pathologies including Lewy bodies and Lewy neuritis mostly located in presynaptic terminals and in axons of affected nerve cells, respectively (Braak et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Imaging changes associated with cognitive abnormalities in Parkinson’s disease

et al. 2014

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The current study investigates both gray and white matter changes in non-demented Parkinson's disease (PD) patients with varying degrees of mild cognitive deficits and elucidates the relationships between the structural changes and clinical sequelae of PD. Twenty-six PD patients and 15 healthy controls (HCs) were enrolled in the study. Participants underwent T1-weighted and diffusion tensor imaging (DTI) scans. Their cognition was assessed using a neuropsychological battery. Compared with HCs, PD patients showed significant cortical thinning in sensorimotor (left pre-and postcentral gyri) and cognitive (left dorsolateral superior frontal gyrus [DLSFG]) regions. The DLSFG cortical thinning correlated with executive and global cognitive impairment in PD patients. PD patients showed white matter abnormalities as well, primarily in bilateral frontal and temporal regions, which also correlated with executive and global cognitive impairment. These results seem to suggest that both gray and white matter changes in the frontal regions may constitute an early pathological substrate of cognitive impairment of PD providing a sensitive biomarker for brain changes in PD.

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Section: Discussionmentioning

confidence: 99%

Imaging changes associated with cognitive abnormalities in Parkinson’s disease

et al. 2014

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“…The pathogenesis of sPD is still enigmatic (Foley and Riederer, 1999), but free radicals produced by mitochondrial dysfunction and oxidative stress are thought to play an important role (Youdim and Riederer, 1997;Mizuno et al, 1998;Schapira et al, 1998). Mitochondrial dysfunction in sPD is supported by the findings on complex I (NADH-ubiquinone reductase complex, one of the five enzyme complexes of the inner mitochondrial membrane involved in oxidative phosphorylation) deficiency in the nigro-striatum of the postmortem brain from sPD patients and of complex I inhibition in the substantia nigra of animal PD models produced by treatment with neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; Langston et al, 1983) or the insecticide rotenone (Betarbet et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Cellular and Molecular Mechanisms of Parkinson’s Disease: Neurotoxins, Causative Genes, and Inflammatory Cytokines

2006

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1. Parkinson's disease (PD) is considered to be an aging-related neurodegeneration of catecholamine (CA) systems [typically A9 dopamine (DA) neurons in the substantia nigra and A6 noradrenaline (NA) neurons in the locus coeruleus]. The main symptom is movement disorder caused by a DA deficiency at the nerve terminals of fibers that project from the substantia nigra to the striatum. Most PD is sporadic (sPD) without any hereditary history. sPD is speculated to be caused by some exogenous or endogenous substances that are neurotoxic toward CA neurons, which toxicity leads to mitochondrial dysfunction and subsequent oxidative stress resulting in the programmed cell death (apoptosis or autophagy) of DA neurons. 2. Recent studies on the causative genes of rare familial PD (fPD) cases, such as alpha-synuclein and parkin, suggest that dysfunction of the ubiquitin-proteasome system (UPS) and the resultant accumulation of misfolded proteins and endoplasmic reticulum stress may cause the death of DA neurons. 3. Activated microglia, which accompany an inflammatory process, are present in the nigro-striatum of the PD brain; and they produce protective or toxic substances, such as cytokines, neurotrophins, and reactive oxygen or nitrogen species. These activated microglia may be neuroprotective at first in the initial stage, and later may become neurotoxic owing to toxic change to promote the progression toward the death of CA neurons.4. All of these accumulating evidences on sPD and fPD points to a hypothesis that multiple primary causes of PD may be ultimately linked to a final common signal-transduction pathway leading to programmed cell death, i.e., apoptosis or autophagy, of the CA neurons.

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“…[13,17,19] However, haloperidol has widespread antidopaminergic effects that are not limited to the nigrostriatal pathway, which is the main dopaminergic pathway compromised in PD. [5,6,16]…”

Section: Introductionmentioning

confidence: 99%

Tongue force and timing deficits in a rat model of Parkinson disease

Ciucci

Russell

Schaser

et al. 2011

Behavioural Brain Research

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Deficits in tongue function in conjunction with airway compromise can contribute to dysphagia associated with Parkinson disease (PD). However, it is unknown if these deficits are related to the primary disease pathology in PD, nigrostriatal dopamine depletion. To directly study the impact of striatal dopamine depletion on tongue function, we used unilateral infusion of the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle and measured tongue force and timing parameters during a complex tongue protrusion task for a water reward. Maximal and average forces were significantly diminished and average press time was significantly longer after neurotoxin administration, reflecting aspects of bradykinesia and hypokinesia associated with PD. Our findings suggest that even unilateral deficits to the nigrostriatal dopamine system may be contributing to some of the lingual sensorimotor deficits seen in PD. Because previous research in rat models of PD has shown that targeted training of the limb can rescue behavioral deficits and spare striatal dopamine neurons, early intervention for cranial sensorimotor deficits may also be indicated.

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Pathogenesis and preclinical course of Parkinson’s disease

Cited by 42 publications

References 202 publications

Imaging changes associated with cognitive abnormalities in Parkinson’s disease

Imaging changes associated with cognitive abnormalities in Parkinson’s disease

Cellular and Molecular Mechanisms of Parkinson’s Disease: Neurotoxins, Causative Genes, and Inflammatory Cytokines

Tongue force and timing deficits in a rat model of Parkinson disease

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