The role of PI3K/AKT pathway and its therapeutic possibility in Alzheimer's disease / 한양의대학술지

Alzheimer's disease (AD) is the most common form of dementia. Although uncountable clinical trials have been done to develop the treatment of AD, there are a couple of drugs that can be used only for symptomatic treatment. Therefore, many studies based on the amyloid cascade hypothesis and the tauopathy hypothesis are still ongoing. After the failure of numerous huge Phase III clinical trials, arguments on those hypotheses have arisen and efforts to establish other possible therapeutic strategies based on diverse plausible mechanisms associated with AD have been done as well. One of the new therapeutic targets for AD is the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. In this review, questions on the two hypotheses, the definition of the PI3K/AKT pathway, the relationship between the pathway and AD, and the possibility of the modulation of the pathway as a new therapeutic strategy for AD will be discussed briefly.

Overview of symptoms, pathogenesis, diagnosis, treatment, and prognosis of various acquired polyneuropathies / 한양의대학술지

Polyneuropathy includes a lot of diseases damaging peripheral nerves. It shows roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. Polyneuropathy is known to usually begin in the hands and feet and progress to the arms and legs. Sometimes it can involve other parts of the body such as the autonomic nervous system. Lots of causes can induce acute or chronic polyneuropathy, so finding the original cause is most important for the treatment of polyneuropathy. There are too many different types of polyneuropathies to be discussed in this review, so we will discuss some of various acquired polyneuropathies such as diabetic neuropathy, vasculitic neuropathy, alcoholic neuropathy, Vitamin B12 deficiency neuropathy, and drug-induced neuropathy, with special focus on symptoms, pathogenesis, diagnosis, treatment, and prognosis.

Diffusion Weighted Imaging Findings in the Acute Lateral Medullary Infarction

BACKGROUND AND PURPOSE: Negative findings on diffusion-weighted imaging (DWI) does not exclude the possibility of brainstem infarction, particularly in the acute stage of medullary lesion. Our aim was to investigate the false-negative rate of DWI in patients with acute lateral medullary infarction. METHODS: We applied DWI to 26 patients with a clinical diagnosis of lateral medullary infarction within 72 h of the onset. We assessed relationships between initial DWI findings and time-to-MRI (the time between onset of symptoms and initial DWI), number of clinical symptoms and signs, and final lesion volume. RESULTS: There were 8 cases (31%) of false negatives in the initial DWI results. The occurrence of false-negative DWI findings decreased significantly as the time-to-MRI increased (P=0.014). However, the false-negative rate was not significantly correlated with the number of clinical symptoms and signs or the final lesion volume. CONCLUSIONS: The diagnosis of lateral medullary infarction should not be ruled out on the basis of early negative DWI. To confirm the lesion, follow-up DWI or further MRI should be performed in cases with early negative DWI results

A Case of Ocular Flutter after Left Medial Medullary Infarction

No abstract available.

Diallyl Disulfide Inhibits Cytochrome c-Mediated Apoptosis in H2O2 Induced Death of Neuronal-differentiated PC12 Cells

BACKGROUND: The effects of diallyl disulfide (DADS), a garlic derived compound, on the viability and cell signaling- like the downstream signaling through cytochrome c, caspase-3, poly (ADP-ribose) polymerase (PARP) during an oxidative-stress induced injury were studied using H2O2 treated neuronal-differentiated PC12 cells by a nerve growth factor. METHODS: To evaluate the toxicity of the DADS itself, the viability of the differentiated PC12 cells treated with several concentrations of DADS was evaluated with 3, (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. To evaluate the protective effect of the low concentration of DADS from oxidative stress, the viability of the cells (DADS pretreated vs. not pretreated) was evaluated following the exposure to 100 micro M H2O2. Additionally, the expression of caspase-3, PARP, and cytochrome c was examined using western blot analyses. RESULTS: The viability was not affected at low concentrations of DADS, up to 20 micro M, but, over this concentration, it was decreased. Compared with the cells treated with only 100 micro M H2O2, the pretreatment with low concentrations of DADS before exposure to 100 micro M H2O2 increased the viability and induced the inhibition of caspase-3 activation, PARP cleavage, and cytochrome c release. CONCLUSIONS: These results show that low concentrations of DADS shows neuroprotective effects by affecting the downstream signaling through cytochrome c, caspase-3, and PARP pathway and may be a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury.

Cytoprotective Effect of Epigallocatechin gallate (EGCG) in Oxidative-stressed PC12 Cells Following H2O2 Exposure-Effect of EGCG on Phosphoinositide 3-kinase/Akt and Glycogen Synthase Kinase-3 Pathway

BACKGROUND: Neurodegenerative diseases (ND) are associated with oxidative stress, and antioxidants including epigallocatechin gallate (EGCG) have been tried as potential therapeutic regimens of an experimental model of ND. We performed this study to determine the neuroprotective role of EGCG on up stream and down stream signals in oxidative-stress-injured PC12 cells by exposing them to H2O2. METHODS: Following 100 microM H2O2 exposure, the viability of PC12 cells (not pretreated vs EGCG or z-VAD-fmk pretreated) was evaluated by using a MTT assay. Immunoreactivity (IR) of cytochrome c, caspase-3, poly (ADP-ribose) polymerase (PARP), PI3K/Akt and GSK-3 was examined by using a Western blot. RESULTS: EGCG or z-VAD-fmk pretreated PC12 cells showed increased viability. Dose-dependent inhibition of caspase-3 activation and PARP cleavage was demonstrated by the pretreatment of both agents. However, the inhibition of cytochrome c release was only detected in EGCG pretreated cells. On the pathway through PI3K/Akt and GSK-3, however, the result of a western blot in EGCG pretreated cells showed decreased IR of Akt and GSK-3 and increased IR of p85a PI3K, phosphorylated Akt and GSK-3, and contrasted with that in z-VAD-fmk pretreated cells showing no changes. CONCLUSIONS: These data show that EGCG affects apoptotic pathways through upstream signals including PI3K/Akt and GSK-3 pathways as well as downstream signals including cytochrome c and caspase-3 pathways. Therefore, these results suggest that EGCG mediated activation of PI3K/Akt and inhibition GSK-3 could be a new protective mechanism on the pathogenesis of ND.

A Case of Tuberculous Meningoencephalitis Presenting as Prominent Psychotic Features / 결핵

Intracranial vasculitis is a rare and disastrous complication of tuberculous meningitis if not treated properly. Focal neurologic deficits according to the vessels involved are common manifestation. Here, we report a 29-year-old man who suffered abrupt, bizarre behavioral changes caused by vasculitis complicating tuberculous meningoencephalitis. The diagnosis of tuberculous meningitis is based upon both the CSF findings and a chest X-ray. His systemic symptoms disappeared by after being administered antituberculous medication but various psychotic features such as hypersomnia, hyperphagia and aggressivebehavior continued. A brain MRI showed multiple small parenchymal tuberculous nodules, and the brain MR angiography revealed a narrowing of the proimal middle cerebral arteries and a reduced visualization of the cerebral vessels, suggesting widespread vasculitis. Intravenous dexamethasone successfully ameliorated his behavioral changes. In addition both the follow up brain MRI and angiography showed a normalization of the previous findings.

A Case of Primary Lateral Sclerosis Showing Degeneration ofCorticospinal Tract on Magnetic Resonance Imaging

Primary lateral sclerosis (PLS) is a rare upper motor neuron disease characterized by selective degeneration of corticospinal and corticobulbar tracts. It is important to rule out other diseases presenting as progressive spastic paraparesis, such as multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS). Though that is not so difficult as the development of imaging technique and neurophysiological tool, if one shows slow progressive spastic paraparesis clinically, and there is no abnormal CSF or EMG findings, it is not easy to differentiate between primary progressive MS and PLS. In fact, PLS is so rare that it has long been debated whether PLS is a disease entity or syndrome or a nothing. But we present a PLS patient whose brain MRI shows diffuse signal change along the bilateral corticospinal tracts and the hypoperfusion of frontal motor cortex is proved by brain SPECT.