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Cyclin-dependent kinase (Cdk) 5 is a unique member of the Cdk family, because Cdk5 kinase activity is detected only in the nervous tissue. Two neuron-specific activating subunits of Cdk5, p35 and p39, have been identified. Overlapping expression pattern of these isoforms in the embryonic mouse brain and the significant residual Cdk5 kinase activity in brain(More)
The mammalian cerebral cortex consists of six layers that are generated via coordinated neuronal migration during the embryonic period. Recent studies identified specific phases of radial migration of cortical neurons. After the final division, neurons transform from a multipolar to a bipolar shape within the subventricular zone-intermediate zone (SVZ-IZ)(More)
In the developing brain, the organization of the neuroepithelium is maintained by a critical balance between proliferation and cell-cell adhesion of neural progenitor cells. The molecular mechanisms that underlie this are still largely unknown. Here, through analysis of a conditional knockout mouse for the Kap3 gene, we show that post-Golgi transport of(More)
BACKGROUND Multiple system atrophy (MSA) has been considered a sporadic disease, without patterns of inheritance. OBJECTIVE To describe the clinical features of 4 multiplex families with MSA, including clinical genetic aspects. DESIGN Clinical and genetic study. SETTING Four departments of neurology in Japan. Patients Eight patients in 4 families with(More)
Cyclin-dependent kinase 5 (Cdk5) is essential for the proper development of the CNS, as is evident from the perinatal lethality of conventional Cdk5 knockout (Cdk5-/-) mice. Cdk5 is also implicated in numerous complex functions of the adult CNS such as synaptic transmission, synaptic plasticity, and neuronal signaling. To elucidate the molecular roles of(More)
Neuronal migration disorders are often identified in patients with epilepsy refractory to medical treatment. The prolonged or repeated seizures are known to cause neuronal death; however, the mechanism underlying seizure-induced neuronal death remains to be elucidated. An essential role of cyclin-dependent kinase 5 (Cdk5) in brain development has been(More)
Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase, and its kinase activity is dependent upon its association with either of the activating subunits p35 or p39, which are mainly expressed in neurons. We previously reported that Cdk5 knockout (KO) mice exhibit perinatal lethality, defective neuronal migration, and abnormal positioning of neurons(More)
Gene targeting to disrupt gene expression in a temporal and spatial manner in a specific tissue using Cre recombinase-mediated gene inactivation has been proven to be useful to study in vivo gene function. To delete genes specifically in neurons during the late phase of brain development, we have generated transgenic mouse lines that express Cre recombinase(More)
BACKGROUND Our previous randomized double-blind study showed that drinking hydrogen (H2) water for 48 weeks significantly improved the total Unified Parkinson's Disease Rating Scale (UPDRS) score of Parkinson's disease (PD) patients treated with levodopa. We aim to confirm this result using a randomized double-blind placebo-controlled multi-center trial. (More)
INTRODUCTION In the mammalian brain, neurons settle into six layers within the cerebral cortex in an inside-out manner, with the earliest-generated neurons positioned in the deepest layers and later-generated neurons occupying the more superficial layers (Angevine and Sidman, 1961). This unique layering is achieved via coordinated radial migration of(More)