Xiongwei Zhu

..Immunocytochemical examination revealed considerable overlap between mGluR2 and neurofibrillary alterations. Thus, it is likely that mGluR2 represents a novel therapeutic target for AD...

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..Taken together, these studies suggest that DJ-1 is involved in the regulation of mitochondrial dynamics through modulation of DLP1 expression and PD-associated DJ-1 mutations may cause PD by impairing mitochondrial dynamics and function...

..These findings directly implicate lipid crosslinking peroxidation products as accumulating not in the lesions or the lipofuscin pathways, but instead in a distinct pathway, GVD, that accumulates cytosolic proteins...

..This is the first finding to our knowledge that CD74 is increased in neurons of AD cases compared to age-matched control cases...

..In this review, we present the evidence for oxidative stress in Alzheimer's disease and its likely sources and consequence in relation to other pathological changes...

..Taken together, these series of results suggest that Bcl-w may play an important protective role in neurons in the diseased brain and that this aspect could be therapeutically harnessed to afford neuroprotection...

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..Taken together, the differential modulation of the MAPK pathways may be critical for neuroprotection of AGS necessary for fluctuations in oxygen and nutrient delivery during hibernation...

..Taken together, these data suggest that p38 is a key downstream effector of amyloid-beta-induced neuronal death and blocking this pathway may be of therapeutic value...

..In light of the known interaction of FOXO3 and 14-3-3, basic protein-protein interaction between these proteins and alpha-synuclein may be key...

..We here discuss the role of mitochondrial dynamics in AD and PD and assess the need for their therapeutic exploitation...

..We here elaborate on the roles of iron, copper, and zinc in AD and describe the therapeutic implications they present...

..Based on these findings, we suggest that an altered balance in mitochondrial fission and fusion is likely an important mechanism leading to mitochondrial and neuronal dysfunction in AD brain...

..The findings presented here suggest that dysregulation of the cell cycle plays a crucial role in the pathogenesis of Alzheimer's disease that may provide a novel mechanistic basis for therapeutic intervention...

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..Additionally, our findings lend support to the notion that tau phosphorylation is a neuroprotective antioxidant response to cellular insults...

..Overall, this study demonstrated that impaired mitochondrial biogenesis likely contributes to mitochondrial dysfunction in AD...

..Overall, these findings suggest that DLP1-dependent mitochondrial fragmentation plays a crucial role in mediating MPP(+) -induced mitochondria abnormalities and cellular dysfunction and may represent a novel therapeutic target for PD...

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..e. mitochondrial protection) that has the potential to significantly deter AD progression if adequately developed. Current treatment strategies under investigation are described in this review...

..Whether increased autophagocytosis is a consequence of an increased turnover of mitochondria or whether the mitochondria in Alzheimer disease are more susceptible to autophagy remains to be resolved...

..Biochemical findings show that tau oxidative modifications are regulated by phosphorylation and that tau found in neurofibrillary tangles is oxidatively modified, suggesting that tau is closely linked to the biology, not toxicity, of AD...

..Based on these findings, we speculate that Raf-1 is activated to effectively mediate Ras-dependent signals in Alzheimer's disease...

..In this review, we present the evidence of oxidative stress and compensatory responses that occur in Alzheimer's disease with a particular focus on the roles and mechanism of activation of stress-activated protein kinase pathways...

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..We concluded that LRRK2 regulates mitochondrial dynamics by increasing mitochondrial DLP1 through its direct interaction with DLP1, and LRRK2 kinase activity plays a critical role in this process...

..Therefore, the study of aberrant cell cycle regulation in model systems, both cellular and animal, may provide extremely important insights into the pathogenesis of AD and also serve as a means to test novel therapeutic approaches...

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..Our data suggest that, despite its upregulation, the aberrant localization of p130 to the neuronal cytoplasm facilitates neuronal cell cycle re-entry in AD...

..These findings suggest that Alzheimer disease is associated with a novel balance in oxidant homeostasis...

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..Therefore, therapeutic interventions targeted toward ameliorating mitotic changes would be predicted to have a profound and positive impact on Alzheimer disease progression...

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..In this review, the scientific basis for common AD therapeutics as well as the efficacy of these treatments will be discussed...

..Together, these findings lend further credence to the notion that the ERK pathway is dysregulated in AD and also indicate an active role for this pathway in disease pathogenesis...

..The study of autophagy in Alzheimer disease could clarify the mechanisms underlying this neurodegenerative disorder and, eventually, help in the development of new therapeutic strategies...

..In conclusion we suggest that chronic oxidative stress contributes to increased tau phosphorylation in vitro and could play a critical role in neurofibrillary pathology in vivo...

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..Therefore, renewed efforts aimed at elucidating fundamental age-related processes such as oxidative stress and/or inflammatory mediators are warranted...

..Here, we discuss vascular factors in relation to Alzheimer disease and review hypoperfusion as a potential cause by triggering mitochondrial dysfunction and increased oxidative stress initiating the pathogenic process...

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..These observations further implicate aberrant neuronal cell cycle progression in neurodegenerative diseases, particularly tauopathies, and suggest a novel target for therapeutic intervention...

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..These findings are the first to demonstrate that PrP(C) is required for Aβ oligomer-induced neuronal cell death, the pathology essential to cognitive loss...

..Although much data remain to be collected, the broad spectrum of changes found in AD are only seen, albeit to a lesser extent, in normal aging with other neurodegenerative diseases showing distinct spectrums of change...

..In this review, we elaborate on the dynamic role of oxidative stress in AD and present corresponding treatment strategies that are currently under investigation...

..In this review, we consider the wealth of evidence implicating a central role for metals in Alzheimer disease...

..Overall, these data strongly suggest that ERK plays an essential role in ONE-mediated cytotoxicity and that ERK is an upstream component of p53-mediated apoptosis...

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..An acceptance that lesion-based therapies do not address etiology or rate-limiting pathogenic factors is probably necessary for the best chance of significant advances that have thus far been elusive...

..Current hypotheses for the pathogenesis of AD are discussed in this review, with a particular emphasis on the implications of these hypotheses with respect to treatment strategies and preventive measures...

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..Therefore, therapeutics targeted toward initiators of the cell cycle are likely to prove of great efficacy for the treatment of AD...

..The possibility that oxidative stress is a primary event in AD indicates that antioxidant-based therapies are perhaps the most promising weapons against this devastating neurodegenerative disorder...

..These findings provide a potential novel protective strategy to treat menopause/age-related cognitive decline and/or prevent the development of AD...

..These data suggest a hindrance in importin-mediated cytoplasmic-nuclear transport in AD...

..Therefore, the aberrant cytoplasmic localization of phosphorylated histone H3 indicates a mitotic catastrophe that leads to neuronal dysfunction and neurodegeneration in AD...

..To determine which hypothesis relates best to Alzheimer disease requires a broader view of disease pathogenesis and is discussed herein...

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..016). These findings suggest that reduction in microtubule assembly is not dependent on tau abnormalities of AD and aging...

..Together, these findings lend further credence to the notion that the JNK/SAPK pathway is dysregulated in AD and also indicate an active role for this pathway in disease pathogenesis...

..Overall, this study demonstrated specific alterations in c-Jun phosphorylation and distribution in AD which is not necessarily linked to apoptosis but rather may represent an adaptation process in the face of oxidative stress...

..Mutations in leucine-rich repeat kinase 2 (LRRK2) are thus far the most frequent genetic cause associated with autosomal dominant and idiopathic Parkinson's disease...

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..e., tau phosphorylation and amyloid-beta deposition, as well as the functional association to amyloid beta protein precursor. We suggest that regulation of these pathways may be a central facet to any potential treatment for the disease...

..In this article, we discuss the multiple pathogenic mechanisms of oxidative stress in AD and the potential targeting approaches...

..This review discusses the concept of abortosis in relation to Alzheimer's disease...

..Based on these findings, we propose that the phosphorylation of tau is a direct consequence of the oxidative stress-induced activation of mitogen-activated protein kinases, including p38...

..Supporting this, the authors have considerable in vivo and in vitro evidence for mitotic disturbances in AD...

..However, this rationale may be misguided since new evidence from our laboratories and others suggest that the lesions not only occur as a by-product of the fundamental disease process but also that they may be protective...

..These findings bring into serious doubt the validity of the Amyloid Cascade Hypothesis as the central cause of Alzheimer disease and, consequently, the potential usefulness of therapeutic targets against amyloid-beta...

..With this in mind, we suspect that current therapeutic efforts targeted toward lowering amyloid-beta production or removal of deposited amyloid-beta will only serve to exacerbate the disease process...

..Although this work indicated the interaction of Aβ42 with huPrP in the AD brain, the pathophysiological relevance of the iPrP/Aβ42 interaction remains to be established...

..Based on this discussion, we propose that mitochondrial dynamics could be a potential therapeutic target for AD...

..Iron deposition at the preclinical stage of AD may be useful as a diagnostic tool, using iron imaging methods, as well as a potential therapeutic target, through metal ion chelators...

..Therefore, cognitive improvements afforded by polyphenolic-rich fruits such as blueberries appear, in part, to be mediated by their effects on hippocampal plasticity...

..Here, we review the role that amyloid-beta plays in mitochondrial structure and function of neurons and the importance of this in the pathogenesis of Alzheimer disease...

..Here, we review the actions of retinoic acid that indicate that it may have therapeutic properties ideally served for the treatment of neurodegenerative diseases such as Alzheimer's disease...

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..However, in the initial stages of disease development, neurons adapt to the oxidative environment through the development of compensatory responses resulting in a shift of neuronal priority from normal function to basic survival...

..As such, therapeutic modalities encompassing antioxidants may be an effective approach to the treatment of neurodegenerative diseases and delay the aging process...

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..In this review, we discuss the role of iron in the progression of AD...

..These results suggest that Arctic ground squirrels experience and tolerate endogenous hypoxia during euthermy and arousal...

..Currently, antioxidant strategies appear to be the most encouraging therapeutics in reducing the clinical manifestation and evolution of Alzheimer's disease...

..Thus, leptin, which ameliorates both amyloid beta and tau-related pathological pathways, holds promise as a novel therapeutic for Alzheimer's disease...

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..In this paper, we summarise evidence for oxidative stress and abnormal mitotic alterations in AD and explain the two-hit hypothesis by describing how both mechanisms are necessary and invariant features of disease...

..We further demonstrate that elevated oxidative stress and increased amyloid beta production are likely the potential pathogenic factors that cause DLP1 reduction and abnormal mitochondrial distribution in AD cells...

..In this review, we weigh the evidence of whether removal of amyloids, aggregates and neuronal inclusions represent a reasonable strategy for protecting neurons...

..Our findings suggest a mechanism by which OS induces BACE1 transcription, thereby promoting production of pathological levels of amyloid beta in AD...

..These data suggest mitochondria are important in oxidative damage that occurs in AD. As such, antioxidant therapies based on lipoic acid and N-acetyl cysteine supplementation may be promising...

..Aim 3: Determine the effect of metal ion chelation on Ab-induced JNK activation. Aim 4: Determine whether H2O2 mediates metal-augmented AB-induced JNK activation. ..

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..Aim 3: Determine the effect of metal ion chelation on Ab-induced JNK activation. Aim 4: Determine whether H2O2 mediates metal-augmented AB-induced JNK activation. ..

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