Author
Ken-ichi Tanaka
Other affiliations: Shujitsu University, Saitama Medical University
Bio: Ken-ichi Tanaka is an academic researcher from Okayama University. The author has contributed to research in topics: Hippocampus & Cholinergic. The author has an hindex of 23, co-authored 50 publications receiving 1684 citations. Previous affiliations of Ken-ichi Tanaka include Shujitsu University & Saitama Medical University.
Topics: Hippocampus, Cholinergic, Striatum, Ischemia, Dopaminergic
Papers
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TL;DR: In vitro free radical scavenging and antioxidant activities of ropinirole, a non-ergot DA agonist, as well as its glutathione, catalase and superoxide dismutase activating effects and neuroprotective effect in vivo are assessed to indicate that activation of GSH, catAlase and SOD mediated via DA D2 receptors may be the principal mechanism of neuroprotection by roPinirole.
207 citations
TL;DR: Bromocriptine has a neuroprotective effect against neurotoxins such as 6-hydroxydopamine, probably due, in part, to its hydroxyl radical scavenging activity and inhibiting effect on dopamine turnover rate, which suggests that early introduction of bromOCriptine in the therapy of Parkinson's disease may be superior to treatment with L-DOPA alone.
163 citations
TL;DR: The present results suggest that DA and its metabolites containing two hydroxyl residues exert cytotoxicity mainly due to generation of highly reactive quinones.
152 citations
TL;DR: It is suggested that the hypoperfused rat may be useful for the cerebrovascular type dementia model to clarify pathophysiology and cholinergic dysfunctions correlate with discrimination learning disabilities in the hypoperatorfused rats.
83 citations
TL;DR: Results show that TNF-α is increased in thestriatum and substantia nigra in 6-OHDA-injected dopaminergic regions in rats, which finding is similar to the increase in the striatal dopaminergy regions in patients with PD.
78 citations
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TL;DR: A review of the evidence for oxidative stress in neurodegeneration and how this relates to other cellular events can be found in this article, where a growing number of in vitro and in vivo models that emulate human disease pathology is aiding scientists in deciphering just where oxidative stress intersects with other cellular processes.
Abstract: Oxidative stress has long been linked to the neuronal cell death that is associated with certain neurodegenerative conditions. Whether it is a primary cause or merely a downstream consequence of the neurodegenerative process is still an open question, however. The advent of a growing number of in vitro and in vivo models that emulate human disease pathology is aiding scientists in deciphering just where oxidative stress intersects with other cellular events in the emerging roadmap leading to neurodegeneration. Here I review the evidence for oxidative stress in neurodegeneration and how this relates to other cellular events.
1,723 citations
TL;DR: Animal models of PD have yielded some insights into the molecular pathways of neuronal degeneration and highlighted previously unknown mechanisms by which oxidative stress contributes to PD, but therapeutic attempts to target the general state of oxidative stress in clinical trials have failed to demonstrate an impact on disease progression.
Abstract: Oxidative stress plays an important role in the degeneration of dopaminergic neurons in Parkinson's disease (PD). Disruptions in the physiologic maintenance of the redox potential in neurons interfere with several biological processes, ultimately leading to cell death. Evidence has been developed for oxidative and nitrative damage to key cellular components in the PD substantia nigra. A number of sources and mechanisms for the generation of reactive oxygen species (ROS) are recognized including the metabolism of dopamine itself, mitochondrial dysfunction, iron, neuroinflammatory cells, calcium, and aging. PD causing gene products including DJ-1, PINK1, parkin, alpha-synuclein and LRRK2 also impact in complex ways mitochondrial function leading to exacerbation of ROS generation and susceptibility to oxidative stress. Additionally, cellular homeostatic processes including the ubiquitin-proteasome system and mitophagy are impacted by oxidative stress. It is apparent that the interplay between these various mechanisms contributes to neurodegeneration in PD as a feed forward scenario where primary insults lead to oxidative stress, which damages key cellular pathogenetic proteins that in turn cause more ROS production. Animal models of PD have yielded some insights into the molecular pathways of neuronal degeneration and highlighted previously unknown mechanisms by which oxidative stress contributes to PD. However, therapeutic attempts to target the general state of oxidative stress in clinical trials have failed to demonstrate an impact on disease progression. Recent knowledge gained about the specific mechanisms related to PD gene products that modulate ROS production and the response of neurons to stress may provide targeted new approaches towards neuroprotection.
1,171 citations
TL;DR: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL)and some forms of cerebral amyloid angiopathy have a genetic basis.
Abstract: Summary Vascular dementia is the second most common type of dementia. The subcortical ischaemic form (SIVD) frequently causes cognitive impairment and dementia in elderly people. SIVD results from small-vessel disease, which produces either arteriolar occlusion and lacunes or widespread incomplete infarction of white matter due to critical stenosis of medullary arterioles and hypoperfusion (Binswanger's disease). Symptoms include motor and cognitive dysexecutive slowing, forgetfulness, dysarthria, mood changes, urinary symptoms, and short-stepped gait. These manifestations probably result from ischaemic interruption of parallel circuits from the prefrontal cortex to the basal ganglia and corresponding thalamocortical connections. Brain imaging (computed tomography and magnetic resonance imaging) is essential for correct diagnosis. The main risk factors are advanced age, hypertension, diabetes, smoking, hyperhomocysteinaemia, hyperfibrinogenaemia, and other conditions that can cause brain hypoperfusion such as obstructive sleep apnoea, congestive heart failure, cardiac arrhythmias, and orthostatic hypotension. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) and some forms of cerebral amyloid angiopathy have a genetic basis. Treatment is symptomatic and prevention requires control of treatable risk factors.
963 citations
TL;DR: The strongest direct evidence that chronic neuroinflammation may have a more important role to play in PD versus other neurodegenerative diseases is reviewed and genetic deficiency is not the only way to reduce protective factors in the brain which may function to keep microglial responses in check or regulate the sensitivity of DA neurons are proposed.
889 citations
TL;DR: In this paper, the authors concluded that sporadic (nongenetic) AD is primarily a vascular rather than a neurodegenerative disorder, based on epidemiological studies showing that practically all risk factors for AD reported thus far have a vascular component that reduces cerebral perfusion.
Abstract: Background— The main stumbling block in the clinical management and in the search for a cure of Alzheimer disease (AD) is that the cause of this disorder has remained uncertain until now. Summary of Review— Evidence that sporadic (nongenetic) AD is primarily a vascular rather than a neurodegenerative disorder is reviewed. This conclusion is based on the following evidence: (1) epidemiological studies showing that practically all risk factors for AD reported thus far have a vascular component that reduces cerebral perfusion; (2) risk factor association between AD and vascular dementia (VaD); (3) improvement of cerebral perfusion obtained from most pharmacotherapy used to reduce the symptoms or progression of AD; (4) detection of regional cerebral hypoperfusion with the use of neuroimaging techniques to preclinically identify AD candidates; (5) presence of regional brain microvascular abnormalities before cognitive and neurodegenerative changes; (6) common overlap of clinical AD and VaD cognitive symptoms; ...
795 citations