scholarly journals COMMENTARY: COMBINATION THERAPY FOR ALZHEIMER’S DISEASE – THE NEXT STEP

2019 ◽  
pp. 1-1
Author(s):  
F. Jessen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Combination Therapy ◽  
Effect Size ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Molecular Target ◽  
Positive Signal ◽  
Clinical Worsening

Over the last several years, many clinical trials in Alzheimer’s disease (AD) have failed and in those with a positive signal, the effect size was of limited magnitude. It has become clear that the molecular mechanisms, which underlie neuronal damage and clinical worsening in AD are complex; maybe even too complex to be sufficiently impacted upon by a single molecular target approach. As in many other diseases, combination therapy might be a way forward to in achieve effects, which eventually are large enough to robustly prove efficacy and to provide patient related benefit.

Enhancing Therapeutic Efficacy of Donepezil by Combined Therapy; A Comprehensive Review

2020 ◽  
Vol 26 ◽  
Author(s):  
Xi Rong ◽  
Liwei Jiang ◽  
Meijie Qu ◽  
Syed Shams ul Hassan ◽  
Zongchao Liu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Combination Therapy ◽  
Dominant Role ◽  
Combined Therapy ◽  
Acetylcholinesterase Inhibitor ◽  
Symptomatic Relief ◽  
Current Status ◽  
Disease Modifying Agents

: Combination therapy involving different therapeutic strategies mostly provides more rapid and effective results as compared to monotherapy in diverse areas of clinical practice. The most worldwide famous acetylcholinesterase inhibitor (AChEIs) donepezil for its dominant role in Alzheimer’s disease (AD) has also attracted the eyes of many pharmaceuticals regarding its promising pharmacological potencies such as neuroprotective, muscle relaxant, and sleep. Recently a combination of donepezil with other agents has displayed better desirable results in the management of several disorders, including most common Alzheimer’s disease (AD). This study encircles all the data regarding the therapeutic effect of donepezil in its combination with other agents and explains its therapeutic targets, mode of action. Furthermore, this review also puts light on the current status of donepezil with other agents in clinical trials. The combo therapy of donepezil with symptomatic relief drugs and disease-modifying agents opens a new road for the treatment of multiple pathological disorders. To best known to our knowledge, this is the first report encircling all the pharmacologic effects of donepezil in its combination therapy with other agents and their current status in clinical trials.

The Neuroprotective and Neurodegeneration Effects of Heme Oxygenase-1 in Alzheimer’s Disease

2020 ◽  
Vol 78 (4) ◽  
pp. 1259-1272
Author(s):  
Zizhen Si ◽  
Xidi Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Heme Oxygenase 1 ◽  
Molecular Processes ◽  
Disease Modifying Therapies

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by complex pathological and biological features. Notably, extracellular amyloid-β deposits as senile plaques and intracellular aggregation of hyperphosphorylated tau as neurofibrillary tangles remain the primary premortem criterion for the diagnosis of AD. Currently, there exist no disease-modifying therapies for AD, and many clinical trials have failed to show its benefits for patients. Heme oxygenase 1 (HO-1) is a 32 kDa enzyme, which catalyzes the degradation of cellular heme to free ferrous iron, biliverdin, and carbon monoxide under stressful conditions. Several studies highlight the crucial pathological roles of HO-1 in the molecular processes of AD. The beneficial roles of HO-1 overexpression in AD brains are widely accepted due to its ability to convert pro-oxidant heme to biliverdin and bilirubin (antioxidants), which promote restoration of a suitable tissue redox microenvironment. However, the intracellular oxidative stress might be amplified by metabolites of HO-1 and exacerbate the progression of AD under certain circumstances. Several lines of evidence have demonstrated that upregulated HO-1 is linked to tauopathies, neuronal damage, and synapse aberrations in AD. Here, we review the aspects of the molecular mechanisms by which HO-1 regulates AD and the latest information on the pathobiology of AD. We further highlight the neuroprotective and neurodystrophic actions of HO-1 and the feasibility of HO-1 as a therapeutic target for AD.

COMBINATION THERAPY FOR ALZHEIMER’S DISEASE: PERSPECTIVES OF THE EU/US CTAD TASK FORCE

2019 ◽  
pp. 1-5
Author(s):  
S. Gauthier ◽  
J. Alam ◽  
H. Fillit ◽  
T. Iwatsubo ◽  
H. Liu-Seifert ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
European Union ◽  
Clinical Trials ◽  
Combination Therapy ◽  
Successful Treatment ◽  
Task Force ◽  
The European Union ◽  
Accelerate Development ◽  
The Eu

Combination therapy is expected to play an important role for the treatment of Alzheimer’s disease (AD). In October 2018, the European Union-North American Clinical Trials in Alzheimer’s Disease Task Force (EU/US CTAD Task Force) met to discuss scientific, regulatory, and logistical challenges to the development of combination therapy for AD and current efforts to address these challenges. Task Force members unanimously agreed that successful treatment of AD will likely require combination therapy approaches that target multiple mechanisms and pathways. They further agreed on the need for global collaboration and sharing of data and resources to accelerate development of such approaches.

Coenzyme Q10:A Review of Its Promise as a Neuroprotectant

CNS Spectrums ◽  
2007 ◽  
Vol 12 (1) ◽  
pp. 62-68 ◽  
Author(s):  
A. Joyce Young ◽  
Stephanie Johnson ◽  
David C. Steffens ◽  
P. Murali Doraiswamy
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Coenzyme Q10 ◽  
Neuronal Damage ◽  
Pilot Trial ◽  
Experimental Studies ◽  
Inner Mitochondrial Membrane

ABSTRACTCoenzyme Q10 (CoQ10) is a powerful antioxidant that buffers the potential adverse consequences of free radicals produced during oxidative phosphorylation in the inner mitochondrial membrane. Oxidative stress, resulting in glutathione loss and oxidative DNA and protein damage, has been implicated in many neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Experimental studies in animal models suggest that CoQ10 may protect against neuronal damage that is produced by ischemia, atherosclerosis and toxic injury. Though most have tended to be pilot studies, there are published preliminary clinical trials showing that CoQ10 may offer promise in many brain disorders. For example, a 16-month randomized, placebo-controlled pilot trial in 80 subjects with mild Parkinson's disease found significant benefits for oral CoQ10 1,200 mg/day to slow functional deterioration. However, to date, there are no published clinical trials of CoQ10 in Alzheimer's disease. Available data suggests that oral CoQ10 seems to be relatively safe and tolerated across the range of 300–2,400 mg/day. Randomized controlled trials are warranted to confirm CoQ10's safety and promise as a clinically effective neuroprotectant.

Neuroprotective Effects of Ellagic Acid in Alzheimer's Disease: Focus on Underlying Molecular Mechanisms of Therapeutic Potential

2020 ◽  
Vol 26 ◽  
Author(s):  
Nimra Javaid ◽  
Muhammad Ajmal Shah ◽  
Azhar Rasul ◽  
Zunera Chauhdary ◽  
Uzma Saleem ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ellagic Acid ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Therapeutic Potential ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Acetylcholinesterase Activity ◽  
Neuroprotective Effects

: Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead towards neuronal cell death. Alzheimer’s disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset yet later on it worsens. The documented evidence of AD neuropathology manifested the neuro-inflammation, increased reactive oxygen, nitrogen species and decreased antioxidant protective process; mitochondrial dysfunction as well as increased level of acetylcholinesterase activity. Moreover, enhanced action of proteins leads towards neural apoptosis which have a vital role in the degeneration of neurons. The inability of commercial therapeutic options to treat AD with targeting single mechanism leads the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid, latest studies expressed that ellagic acid can initiate the numerous cell signaling transmission and decrease the progression of disorders, involved in the degeneration of neurons. The influential property of ellagic acid to protect the neurons in neurodegenerative disorders is due to its antioxidant effect, iron chelating and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mode of action of ellagic acid against neurodegeneration.

Identifying Alzheimer’s Disease-related miRNA Based on Semi-clustering

2019 ◽  
Vol 19 (4) ◽  
pp. 216-223 ◽  
Author(s):  
Tianyi Zhao ◽  
Donghua Wang ◽  
Yang Hu ◽  
Ningyi Zhang ◽  
Tianyi Zang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Feature Vector ◽  
Mirna Gene ◽  
Interaction Network ◽  
Gene Interaction ◽  
Proteinprotein Interaction ◽  
Synaptic Structures

Background: More and more scholars are trying to use it as a specific biomarker for Alzheimer’s Disease (AD) and mild cognitive impairment (MCI). Multiple studies have indicated that miRNAs are associated with poor axonal growth and loss of synaptic structures, both of which are early events in AD. The overall loss of miRNA may be associated with aging, increasing the incidence of AD, and may also be involved in the disease through some specific molecular mechanisms. Objective: Identifying Alzheimer’s disease-related miRNA can help us find new drug targets, early diagnosis. Materials and Methods: We used genes as a bridge to connect AD and miRNAs. Firstly, proteinprotein interaction network is used to find more AD-related genes by known AD-related genes. Then, each miRNA’s correlation with these genes is obtained by miRNA-gene interaction. Finally, each miRNA could get a feature vector representing its correlation with AD. Unlike other studies, we do not generate negative samples randomly with using classification method to identify AD-related miRNAs. Here we use a semi-clustering method ‘one-class SVM’. AD-related miRNAs are considered as outliers and our aim is to identify the miRNAs that are similar to known AD-related miRNAs (outliers). Results and Conclusion: We identified 257 novel AD-related miRNAs and compare our method with SVM which is applied by generating negative samples. The AUC of our method is much higher than SVM and we did case studies to prove that our results are reliable.

Sign in / Sign up

Export Citation Format

Share Document