scholarly journals Parkinson’s Disease and Autophagy

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ana María Sánchez-Pérez ◽  
Berta Claramonte-Clausell ◽  
Juan Vicente Sánchez-Andrés ◽  
María Trinidad Herrero
Keyword(s):  
Cell Death ◽  
Animal Models ◽  
Neurodegenerative Disease ◽  
Causal Relationship ◽  
Neurodegenerative Disorders ◽  
Therapeutic Strategy ◽  
Neuroprotective Effects ◽  
Autophagy Induction ◽  
Effective Therapeutic Strategy ◽  
The Brain

It is generally accepted that a correlation between neurodegenerative disease and protein aggregation in the brain exists; however, a causal relationship has not been elucidated. In neurons, failure of autophagy may result in the accumulation of aggregate-prone proteins and subsequent neurodegeneration. Thus, pharmacological induction of autophagy to enhance the clearance of intracytoplasmic aggregate-prone proteins has been considered as a therapeutic strategy to ameliorate pathology in cell and animal models of neurodegenerative disorders. However, autophagy has also been found to be a factor in the onset of these diseases, which raises the question of whether autophagy induction is an effective therapeutic strategy, or, on the contrary, can result in cell death. In this paper, we will first describe the autophagic machinery, and we will consider the literature to discuss the neuroprotective effects of autophagy.

scholarly journals Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2746
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cell ◽  
Liver Cancer ◽  
Signaling Pathways ◽  
Therapeutic Strategy ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Therapeutic Approaches ◽  
Effective Therapeutic Strategy ◽  
Cancer Types ◽  
The Brain

The first report of cancer stem cell (CSC) from Bruce et al. has demonstrated the relatively rare population of stem-like cells in acute myeloid leukemia (AML). The discovery of leukemic CSCs prompted further identification of CSCs in multiple types of solid tumor. Recently, extensive research has attempted to identity CSCs in multiple types of solid tumors in the brain, colon, head and neck, liver, and lung. Based on these studies, we hypothesize that the initiation and progression of most malignant tumors rely largely on the CSC population. Recent studies indicated that stem cell-related markers or signaling pathways, such as aldehyde dehydrogenase (ALDH), CD133, epithelial cell adhesion molecule (EpCAM), Wnt/β-catenin signaling, and Notch signaling, contribute to the initiation and progression of various liver cancer types. Importantly, CSCs are markedly resistant to conventional therapeutic approaches and current targeted therapeutics. Therefore, it is believed that selectively targeting specific markers and/or signaling pathways of hepatic CSCs is an effective therapeutic strategy for treating chemotherapy-resistant liver cancer. Here, we provide an overview of the current knowledge on the hepatic CSC hypothesis and discuss the specific surface markers and critical signaling pathways involved in the development and maintenance of hepatic CSC subpopulations.

scholarly journals The Nasal Route as a Potential Pathway for Delivery of Erythropoietin in the Treatment of Acute Ischemic Stroke in Humans

2009 ◽  
Vol 9 ◽  
pp. 970-981 ◽  
Author(s):  
Julio Cesar García-Rodríguez ◽  
Iliana Sosa Teste
Keyword(s):  
Neurodegenerative Disorders ◽  
Clinical Evidence ◽  
Nasal Administration ◽  
Intranasal Delivery ◽  
Neuroprotective Effects ◽  
Sialic Acid Content ◽  
Chemically Modified ◽  
Different Types ◽  
The Central Nervous System ◽  
The Brain

Intranasal delivery provides a practical, noninvasive method of bypassing the blood-brain barrier (BBB) in order to deliver therapeutic agents to the brain. This method allows drugs that do not cross the BBB to be delivered to the central nervous system in a few minutes. With this technology, it will be possible to eliminate systemic administration and its potential side effects. Using the intranasal delivery system, researchers have demonstrated neuroprotective effects in different animal models of stroke using erythropoietin (EPO) as a neuroprotector or other different types of EPO without erythropoiesis-stimulating activity. These new molecules retain their ability to protect neural tissue against injury and they include Asialoerythropoietin (asialoEPO) carbamylated EPO (CEPO), and rHu-EPO with low sialic acid content (Neuro-EPO). Contrary to the other EPO variants, Neuro-EPO is not chemically modified, making it biologically similar to endogenous EPO, with the advantage of less adverse reactions when this molecule is applied chronically. This constitutes a potential benefit of Neuro-EPO over other variants of EPO for the chronic treatment of neurodegenerative illnesses. Nasal administration of EPO is a potential, novel, neurotherapeutic approach. However, it will be necessary to initiate clinical trials in stroke patients using intranasal delivery in order to obtain the clinical evidence of its neuroprotectant capacity in the treatment of patients with acute stroke and other neurodegenerative disorders. This new therapeutic approach could revolutionize the treatment of neurodegenerative disorders in the 21stcentury.

scholarly journals Glutamate and γ-aminobutyric acid differentially modulate glymphatic clearance of amyloid β through pulsation- and aquaporin-4 dependent mechanisms

2020 ◽  
Author(s):  
Cheng Wu ◽  
Yi-wei Feng ◽  
Qun Zhang ◽  
Feng-yin Liang ◽  
Yue Lan ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Amyloid Β ◽  
Aquaporin 4 ◽  
Aminobutyric Acid ◽  
Dependent Manner ◽  
Ang Ii ◽  
Induced Hypertension ◽  
Effective Therapeutic Strategy ◽  
Glymphatic Pathway ◽  
The Brain

AbstractThe glymphatic system contributes to a large proportion of brain waste clearance, including removal of amyloid β (Aβ). We have demonstrated that glutamate and γ-aminobutyric acid (GABA) influence glymphatic clearance through distinct mechanisms whereby GABA exerts modulatory effects in an aquaporin-4 (AQP4)-dependent manner while the actions of glutamate are pulsation-dependent. The efficacy of GABA and glutamate in alleviating Aβ in APP-PS1 and Angiotensin-II (Ang-II) induced hypertension mouse models was further evaluated. Notably, increasing GABA or inhibiting glutamate levels led to reduced binding of Aβ to pre-labeled plaques to similar extents in APP-PS1 mice while GABA appeared more efficient in Aβ clearance in hypertensive animals than the glutamate inhibitor. Our findings support the modulation of neurotransmitters that influence the glymphatic pathway via distinct mechanisms as a potentially effective therapeutic strategy for clearance of Aβ deposits from the brain.

scholarly journals TH24. INVESTIGATION OF THE CAUSAL RELATIONSHIP BETWEEN IRON ACCUMULATION IN THE BRAIN AND NEURODEGENERATIVE DISEASE

2021 ◽  
Vol 51 ◽  
pp. e207-e208
Author(s):  
Michelle Lupton ◽  
Zachary Gerring ◽  
Eske Derks ◽  
Stuart MacGregor ◽  
Jue-Sheng Ong ◽  
...  
Keyword(s):  
Neurodegenerative Disease ◽  
Causal Relationship ◽  
Iron Accumulation ◽  
The Brain

Animal Models of Neurodegenerative Diseases

2016 ◽  
Author(s):  
David Baglietto-Vargas ◽  
Rahasson R. Ager ◽  
Rodrigo Medeiros ◽  
Frank M. LaFerla
Keyword(s):  
Animal Models ◽  
Life Expectancy ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Human Disease ◽  
Molecular Mechanisms ◽  
Preclinical Studies ◽  
Pathological Features ◽  
The Past ◽  
The Brain

The incidence and prevalence of neurodegenerative disorders (e.g., Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), etc.) are growing rapidly due to increasing life expectancy. Researchers over the past two decades have focused their efforts on the development of animal models to dissect the molecular mechanisms underlying neurodegenerative disorders. Existing models, however, do not fully replicate the symptomatic and pathological features of human diseases. This chapter focuses on animal models of AD, as this disorder is the most prevalent of the brain degenerative conditions afflicting society. In particular, it briefly discusses the current leading animal models, the translational relevance of the preclinical studies using such models, and the limitations and shortcomings of using animals to model human disease. It concludes with a discussion of potential means to improve future models to better recapitulate human conditions.

Heme induces autophagic cell death via ER stress in neuron

2019 ◽  
Author(s):  
Zhao Yang ◽  
ZhongYan Huang ◽  
Bing Tang ◽  
Nan Zhang ◽  
Na Ji
Keyword(s):  
Cell Death ◽  
Er Stress ◽  
Therapeutic Strategy ◽  
Medical Problem ◽  
Vital Role ◽  
Specific Mechanism ◽  
Downstream Effects ◽  
Pharmacologic Inhibitors ◽  
The Relationship ◽  
The Brain

Abstract Aims Intracerebral hemorrhage (ICH) is serious medical problem and the effective treatment is limited. Hemorrhaged blood is highly toxic to the brain, and heme mainly released from hemoglobin plays a vital role in neurotoxicity. However, the specific mechanism involved in heme mediated neurotoxicity has not been well studied.Methods In this study, we investigated the neurotoxicity of heme in neurons. Neurons were administrated with heme, and the cell death, autophagy and ER stress were analyzed. In addition, the relationship between autophagy and apoptosis in heme-induced cell death and the downstream effects were also detected.Results We showed that heme induced cell death and autophagy in neurons. The suppression of autophagy using either pharmacologic inhibitors (3-methyladenine) or RNA interference in essential autophagy genes (BECN1 and ATG5) decreased the cell death induced by heme in neurons. Moreover, ER stress activator thapsigargin increased the cell autophagy and cell death ratio following heme treatment. Autophagy promotes cell apoptosis and cell death induced by heme through BECN1/ ATG5 pathway.Conclusions Our findings suggest that heme potentiates neuron autophagy via ER stress, in turn inducing cell death via BECN1/ATG5 pathway. Targeting ER stress mediated autophagy might be a promising therapeutic strategy for ICH.

scholarly journals Lead, Manganese, and Methylmercury as Risk Factors for Neurobehavioral Impairment in Advanced Age

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Bernard Weiss
Keyword(s):  
Risk Factors ◽  
Adverse Effects ◽  
Neurodegenerative Disease ◽  
Early Development ◽  
Neurodegenerative Disorders ◽  
Advanced Age ◽  
Metal Contaminants ◽  
Aging Populations ◽  
The Brain

Contamination of the environment by metals is recognized as a threat to health. One of their targets is the brain, and the adverse functional effects they induce are reflected by neurobehavioral assessments. Lead, manganese, and methylmercury are the metal contaminants linked most comprehensively to such disorders. Because many of these adverse effects can appear later in life, clues to the role of metals as risk factors for neurodegenerative disorders should be sought in the exposure histories of aging populations. A review of the available literature offers evidence that all three metals can produce, in advanced age, manifestations of neurobehavioral dysfunction associated with neurodegenerative disease. Among the critical unresolved questions is timing; that is, during which periods of the lifespan, including early development, do environmental exposures lay the foundations for their ultimate effects?

scholarly journals Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts

2015 ◽  
Vol 35 (2) ◽  
Author(s):  
Li Sui ◽  
Rui-Hong Zhang ◽  
Ping Zhang ◽  
Ke-Li Yun ◽  
Hong-Cai Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Side Effects ◽  
Therapeutic Strategy ◽  
Lead Toxicity ◽  
Protective Role ◽  
Molecular Processes ◽  
Effective Therapeutic Strategy ◽  
Mtorc1 Pathway ◽  
Set Up

Lead is a metal with many recognized adverse health side effects, and yet the molecular processes in cardiofibroblasts underlying lead toxicity are still poorly understood. Our current findings will help to understand the role of lead-mediated toxicity in cardiofibroblasts, indicating that autophagy serves a protective role in response to ER stress, which affords to set up an effective therapeutic strategy for the numerous diseases related to lead-toxicity.

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