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Ho W.-L.,Laboratory of Neurodegenerative Diseases | Leung Y.,Laboratory of Neurodegenerative Diseases | Tsang A.W.-T.,Laboratory of Neurodegenerative Diseases | Chiu K.,Laboratory of Neurodegenerative Diseases | Chang R.C.-C.,Laboratory of Neurodegenerative Diseases
Molecular Vision | Year: 2012

Tau protein's versatility lies in its functions within the central nervous system, including protein scaffolding and intracellular signaling. Tauopathy has been one of the most extensively studied neuropathologies among the neurodegenerative diseases. Because the retina and optic nerve are parts of the central nervous system, we hypothesize that tauopathy also plays a role in various eye diseases. However, little is known about tauopathy in the retina and optic nerve. Here, we summarize the findings from histopathological studies on animal models and human specimens with distinct neurodegenerative diseases. Similar pathological changes of tau protein can be found in Alzheimer's disease, frontotemporal lobe dementia, and glaucoma. In view of the important roles of tauopathy in the brain, it is hoped that this review can stimulate research on eye diseases of the retina and optic nerve. © 2012 Molecular Vision. Source


Lau C.-F.,Laboratory of Neurodegenerative Diseases | Ho Y.-S.,Laboratory of Neurodegenerative Diseases | Ho Y.-S.,Macau University of Science and Technology | Hung C.H.-L.,Laboratory of Neurodegenerative Diseases | And 8 more authors.
BioMed Research International | Year: 2014

Increasing lines of evidence support that testosterone may have neuroprotective effects. While observational studies reported an association between higher bioavailable testosterone or brain testosterone levels and reduced risk of Alzheimer's disease (AD), there is limited understanding of the underlying neuroprotective mechanisms. Previous studies demonstrated that testosterone could alleviate neurotoxicity induced by β-amyloid (Aβ), but these findings mainly focused on neuronal apoptosis. Since synaptic dysfunction and degeneration are early events during the pathogenesis of AD, we aim to investigate the effects of testosterone on oligomeric Aβ-induced synaptic changes. Our data suggested that exposure of primary cultured hippocampal neurons to oligomeric Aβ could reduce the length of neurites and decrease the expression of presynaptic proteins including synaptophysin, synaptotagmin, and synapsin-1. Aβ also disrupted synaptic vesicle recycling and protein folding machinery. Testosterone preserved the integrity of neurites and the expression of presynaptic proteins. It also attenuated Aβ-induced impairment of synaptic exocytosis. By using letrozole as an aromatase antagonist, we further demonstrated that the effects of testosterone on exocytosis were unlikely to be mediated through the estrogen receptor pathway. Furthermore, we showed that testosterone could attenuate Aβ-induced reduction of HSP70, which suggests a novel mechanism that links testosterone and its protective function on Aβ-induced synaptic damage. Taken together, our data provide further evidence on the beneficial effects of testosterone, which may be useful for future drug development for AD. © 2014 Chi-Fai Lau et al. Source


Wuwongse S.,Laboratory of Neurodegenerative Diseases | Chang R.C.-C.,Laboratory of Neurodegenerative Diseases | Chang R.C.-C.,University of Hong Kong | Law A.C.K.,University of Hong Kong
Progress in Neurobiology | Year: 2010

Alzheimer's disease (AD) is the leading neurodegenerative cause of dementia in the elderly. Thus far, there is no curative treatment for this devastating condition, thereby creating significant social and medical burdens. AD is characterized by progressive cognitive decline along with various neuropsychiatric symptoms, including depression and psychosis.Depression is a common psychiatric disorder affecting individuals across the life span. Although the " monoamine hypothesis" of depression has long been proposed, the pathologies and mechanisms for depressive disorders remain only partially understood. Pharmacotherapies targeting the monoaminergic pathways have been the mainstay in treating depression. Additional therapeutic approaches focusing other pathological mechanisms of depression are currently being explored.Interestingly, a number of proposed mechanisms for depression appear to be similar to those implicated in neurodegenerative diseases, including AD. For example, diminishing neurotrophic factors and neuroinflammation observed in depression are found to be associated with the development of AD. This article first provides a concise review of AD and depression, then discusses the putative links between the two neuropsychiatric conditions. © 2010 Elsevier Ltd. Source


Wong G.T.H.,Neurodysfunction Research Laboratory | Wong G.T.H.,Laboratory of Neurodegenerative Diseases | Chang R.C.C.,Laboratory of Neurodegenerative Diseases | Chang R.C.C.,University of Hong Kong | And 2 more authors.
Ageing Research Reviews | Year: 2013

Depression is one of the most common psychiatric disorders with inadequately understood disease mechanisms. It has long been considered that dendritic regression and decrease in the number of dendritic spines are involved in depression. Dendrites made up of microtubules and actin filaments form synapses with neighboring neurons, which come together as an important communication network. Cytoskeletal proteins undergo post-translational modifications to define their structure and function. In depression and other psychiatric disorders, post-translational modifications may be disrupted that can result in altered cytoskeletal functions. The disruption of microtubule and actin in terms of morphology and functions may be a leading cause of dendritic regression and decrease in dendritic spine in depression. © 2012. Source


Wuwongse S.,Neurodysfunction Research Laboratory | Wuwongse S.,Laboratory of Neurodegenerative Diseases | Cheng S.S.Y.,Laboratory of Neurodegenerative Diseases | Wong G.T.H.,Neurodysfunction Research Laboratory | And 9 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2013

The relationship between Alzheimer's disease (AD) and depression has been well established in terms of epidemiological and clinical observations. Depression has been considered to be both a symptom and risk factor of AD. Several genetic and neurobiological mechanisms have been described to underlie these two disorders. Despite the accumulating knowledge on this topic, the precise neuropathological mechanisms remain to be elucidated. In this study, we propose that synaptic degeneration plays an important role in the disease progression of depression and AD. Using primary culture of hippocampal neurons treated with oligomeric Aβ and corticosterone as model agents for AD and depression, respectively, we found significant changes in the pre-synaptic vesicle proteins synaptophysin and synaptotagmin. We further investigated whether the observed protein changes affected synaptic functions. By using FM®4-64 fluorescent probe, we showed that synaptic functions were compromised in treated neurons. Our findings led us to investigate the involvement of protein degradation mechanisms in mediating the observed synaptic protein abnormalities, namely, the ubiquitin-proteasome system and autophagy. We found up-regulation of ubiquitin-mediated protein degradation, and the preferential signaling for the autophagic-lysosomal degradation pathway. Lastly, we investigated the neuroprotective role of different classes of antidepressants. Our findings demonstrated that the antidepressants Imipramine and Escitalopram were able to rescue the observed synaptic protein damage. In conclusion, our study shows that synaptic degeneration is an important common denominator underlying depression and AD, and alleviation of this pathology by antidepressants may be therapeutically beneficial. © 2013 Elsevier B.V. Source

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