Serotoninergic antidepressants positively affect platelet ADAM10 expression in patients with Alzheimer's disease

2015 ◽  
Vol 28 (6) ◽  
pp. 939-944 ◽  
Author(s):  
Otávio Augusto Fernandes Marques Bianco ◽  
Patrícia Regina Manzine ◽  
Carla Manuela Crispim Nascimento ◽  
Francisco Assis Carvalho Vale ◽  
Sofia Cristina Iost Pavarini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Protein Extraction ◽  
Biological Mechanisms ◽  
Important Advance ◽  
Positive Effects ◽  
Tetracyclic Antidepressants ◽  
Adam10 Expression ◽  
The Central Nervous System

ABSTRACTBackground:Studies have demonstrated a decreased platelet ADAM10 expression in patients with Alzheimer's Disease (AD), classifying this protein as a blood-based AD biomarker. About 50% of the patients with AD are diagnosed with depression, which is commonly treated with tricyclic and tetracyclic antidepressants, monoaminoxidade (MAO) inhibitors and, more preferably, with selective serotonin reuptake inhibitors (SSRIs). Considering that a large proportion of patients with AD takes antidepressant medications during the course of the disease we investigated the influence of this medication on the expression of platelet ADAM10, which is considered the main α-secretase preventing beta-amyloid (βA) formation.Methods:Blood was collected for protein extraction from platelets. ADAM10 was analyzed by using western blotting and reactive bands were measured using β-actin as endogenous control.Results:Platelet ADAM10 protein expression in patients with AD was positively influenced by serotoninergic medication.Conclusion:More studies on the positive effects of serotonergic antidepressants on ADAM10 platelet expression should be performed in order to understand its biological mechanisms and to verify whether these effects are reflected in the central nervous system. This work represents an important advance for the study of AD biomarkers, as well as for more effective pharmacological treatment of patients with AD and associated depression.

Current Research on Pro-Drug Therapies for Parkinson's and Alzheimer's Disease

2021 ◽  
Vol 18 ◽  
Author(s):  
Cui Huo ◽  
Lei Wu ◽  
Zhiqiang Jiang ◽  
Jiacheng Yang ◽  
Zhouyu Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Targeted Drug Delivery ◽  
Relevant Literature ◽  
Research Progress ◽  
Design Strategies ◽  
Biological Mechanisms ◽  
Drug Bioavailability ◽  
The Central Nervous System ◽  
Approved Drugs

: Background: alzheimer's disease (ad) and parkinson's (pd) disease are common neurodegenerative conditions of the central nervous system (cns). Thus, these diseases have only been treated symptomatically since no approved drug is available that provides a complete cure. Objectives: through reading relevant literature published at home and abroad, the method and significance of prodrug strategy to increase the efficacy of ad and pd drugs were discussed. Methods: the biological mechanisms and currently approved drugs for both diseases have been discussed, revealing that most of these treatments utilized existing prodrug design strategies, including increased lipophilicity, and the use of transporters mediation and bio-oxidation to improve oral bioavailability and brain permeability. Results: the purpose of this paper is to review the research progress in the treatment of neurodegenerative diseases (ndds), especially ad and pd, using the prodrug strategy. The research of drug bioavailability and the prodrug strategy of cns targeted drug delivery lay the foundation for drug development to treat these diseases. Conclusion: the use of prodrug strategies provides important opportunities for the development of novel therapies for ad and pd.

Paired helical filaments (PHF) in rats: An experimental animal model for Alzheimer's disease

1987 ◽  
Vol 45 ◽  
pp. 842-843
Author(s):  
V.J.A. Montpetit ◽  
S. Dancea ◽  
S.W. French ◽  
D.F. Clapin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Paired Helical Filaments ◽  
Ethanol Intoxication ◽  
Drg Neurons ◽  
Critical Difference ◽  
Suitable Animal Model ◽  
The Central Nervous System ◽  
Chronic Ethanol Intoxication

A continuing problem in Alzheimer research is the lack of a suitable animal model for the disease. The absence of neurofibrillary tangles of paired helical filaments is the most critical difference in the processes by which the central nervous system ages in most species other than man. However, restricting consideration to single phenomena, one may identify animal models for specific aspects of Alzheimer's disease. Abnormal fibers resembling PHF have been observed in dorsal root ganglia (DRG) neurons of rats in a study of chronic ethanol intoxication and spontaneously in aged rats. We present in this report evidence that PHF-like filaments occur in ethanol-treated rats of young age. In control animals lesions similar in some respects to our observations of cytoskeletal pathology in pyridoxine induced neurotoxicity were observed.Male Wistar BR rats (Charles River Labs) weighing 350 to 400 g, were implanted with a single gastrostomy cannula and infused with a liquid diet containing 30% of total calories as fat plus ethanol or isocaloric dextrose.

Alzheimer’s Disease Targeted Nano-Based Drug Delivery Systems

2020 ◽  
Vol 21 (7) ◽  
pp. 628-646
Author(s):  
Gülcem Altinoglu ◽  
Terin Adali
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Neurological Diseases ◽  
Sustained Drug Release ◽  
Physiochemical Properties ◽  
Conventional Drug ◽  
Health Care Burden ◽  
The Central Nervous System ◽  
Effective Drugs

Alzheimer’s disease (AD) is the most common neurodegenerative disease, and is part of a massive and growing health care burden that is destroying the cognitive function of more than 50 million individuals worldwide. Today, therapeutic options are limited to approaches with mild symptomatic benefits. The failure in developing effective drugs is attributed to, but not limited to the highly heterogeneous nature of AD with multiple underlying hypotheses and multifactorial pathology. In addition, targeted drug delivery to the central nervous system (CNS), for the diagnosis and therapy of neurological diseases like AD, is restricted by the challenges posed by blood-brain interfaces surrounding the CNS, limiting the bioavailability of therapeutics. Research done over the last decade has focused on developing new strategies to overcome these limitations and successfully deliver drugs to the CNS. Nanoparticles, that are capable of encapsulating drugs with sustained drug release profiles and adjustable physiochemical properties, can cross the protective barriers surrounding the CNS. Thus, nanotechnology offers new hope for AD treatment as a strong alternative to conventional drug delivery mechanisms. In this review, the potential application of nanoparticle based approaches in Alzheimer’s disease and their implications in therapy is discussed.

Neuropeptides in Alzheimer’s Disease: An Update

2019 ◽  
Vol 16 (6) ◽  
pp. 544-558 ◽  
Author(s):  
Carla Petrella ◽  
Maria Grazia Di Certo ◽  
Christian Barbato ◽  
Francesca Gabanella ◽  
Massimo Ralli ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Potential Role ◽  
Brain Distribution ◽  
Brain Areas ◽  
Small Proteins ◽  
Current Review ◽  
The Central Nervous System ◽  
Available Information

Neuropeptides are small proteins broadly expressed throughout the central nervous system, which act as neurotransmitters, neuromodulators and neuroregulators. Growing evidence has demonstrated the involvement of many neuropeptides in both neurophysiological functions and neuropathological conditions, among which is Alzheimer’s disease (AD). The role exerted by neuropeptides in AD is endorsed by the evidence that they are mainly neuroprotective and widely distributed in brain areas responsible for learning and memory processes. Confirming this point, it has been demonstrated that numerous neuropeptide-containing neurons are pathologically altered in brain areas of both AD patients and AD animal models. Furthermore, the levels of various neuropeptides have been found altered in both Cerebrospinal Fluid (CSF) and blood of AD patients, getting insights into their potential role in the pathophysiology of AD and offering the possibility to identify novel additional biomarkers for this pathology. We summarized the available information about brain distribution, neuroprotective and cognitive functions of some neuropeptides involved in AD. The main focus of the current review was directed towards the description of clinical data reporting alterations in neuropeptides content in both AD patients and AD pre-clinical animal models. In particular, we explored the involvement in the AD of Thyrotropin-Releasing Hormone (TRH), Cocaine- and Amphetamine-Regulated Transcript (CART), Cholecystokinin (CCK), bradykinin and chromogranin/secretogranin family, discussing their potential role as a biomarker or therapeutic target, leaving the dissertation of other neuropeptides to previous reviews.

Neurobehavioral Consequences Associated with Long Term Tramadol Utilization and Pathological Mechanisms

2020 ◽  
Vol 18 (10) ◽  
pp. 758-768 ◽  
Author(s):  
Khadga Raj ◽  
Pooja Chawla ◽  
Shamsher Singh
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Syndrome ◽  
Dopamine Synthesis ◽  
Synthetic Analog

: Tramadol is a synthetic analog of codeine used to treat pain of moderate to severe intensity and is reported to have neurotoxic potential. At therapeutic dose, tramadol does not cause major side effects in comparison to other opioid analgesics, and is useful for the management of neurological problems like anxiety and depression. Long term utilization of tramadol is associated with various neurological disorders like seizures, serotonin syndrome, Alzheimer’s disease and Parkinson’s disease. Tramadol produces seizures through inhibition of nitric oxide, serotonin reuptake and inhibitory effects on GABA receptors. Extensive tramadol intake alters redox balance through elevating lipid peroxidation and free radical leading to neurotoxicity and produces neurobehavioral deficits. During Alzheimer’s disease progression, low level of intracellular signalling molecules like cGMP, cAMP, PKC and PKA affect both learning and memory. Pharmacologically tramadol produces actions similar to Selective Serotonin Reuptake Inhibitors (SSRIs), increasing the concentration of serotonin, which causes serotonin syndrome. In addition, tramadol also inhibits GABAA receptors in the CNS has been evidenced to interfere with dopamine synthesis and release, responsible for motor symptoms. The reduced level of dopamine may produce bradykinesia and tremors which are chief motor abnormalities in Parkinson’s Disease (PD).

scholarly journals Loss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xin Ding ◽  
Jin Wang ◽  
Miaoxin Huang ◽  
Zhangpeng Chen ◽  
Jing Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Knock Out ◽  
Classical Complement Pathway ◽  
Synaptic Remodeling ◽  
The Central Nervous System ◽  
System Activation ◽  
Knock Out Mice ◽  
Synaptic Pruning

AbstractMicroglia play a key role in regulating synaptic remodeling in the central nervous system. Activation of classical complement pathway promotes microglia-mediated synaptic pruning during development and disease. CD47 protects synapses from excessive pruning during development, implicating microglial SIRPα, a CD47 receptor, in synaptic remodeling. However, the role of microglial SIRPα in synaptic pruning in disease remains unclear. Here, using conditional knock-out mice, we show that microglia-specific deletion of SIRPα results in decreased synaptic density. In human tissue, we observe that microglial SIRPα expression declines alongside the progression of Alzheimer’s disease. To investigate the role of SIRPα in neurodegeneration, we modulate the expression of microglial SIRPα in mouse models of Alzheimer’s disease. Loss of microglial SIRPα results in increased synaptic loss mediated by microglia engulfment and enhanced cognitive impairment. Together, these results suggest that microglial SIRPα regulates synaptic pruning in neurodegeneration.

scholarly journals Brain-Derived Exosomal Proteins as Effective Biomarkers for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 980
Author(s):  
Ka-Young Kim ◽  
Ki-Young Shin ◽  
Keun-A. Chang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Web Of Science ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Blood Biomarkers ◽  
Cell Lineages ◽  
The Central Nervous System ◽  
New Biomarkers ◽  
T Tau

Alzheimer’s disease (AD), a progressive neurodegenerative disease, affects approximately 50 million people worldwide, which warrants the search for reliable new biomarkers for early diagnosis of AD. Brain-derived exosomal (BDE) proteins, which are extracellular nanovesicles released by all cell lineages of the central nervous system, have been focused as biomarkers for diagnosis, screening, prognosis prediction, and monitoring in AD. This review focused on the possibility of BDE proteins as AD biomarkers. The articles published prior to 26 January 2021 were searched in PubMed, EMBASE, Web of Science, and Cochrane Library to identify all relevant studies that reported exosome biomarkers in blood samples of patients with AD. From 342 articles, 20 studies were selected for analysis. We conducted a meta-analysis of six BDE proteins and found that levels of amyloid-β42 (standardized mean difference (SMD) = 1.534, 95% confidence interval [CI]: 0.595–2.474), total-tau (SMD = 1.224, 95% CI: 0.534–1.915), tau phosphorylated at threonine 181 (SMD = 4.038, 95% CI: 2.312-5.764), and tau phosphorylated at serine 396 (SMD = 2.511, 95% CI: 0.795–4.227) were significantly different in patients with AD compared to those in control. Whereas, those of p-tyrosine-insulin receptor substrate-1 and heat shock protein 70 did not show significant differences. This review suggested that Aβ42, t-tau, p-T181-tau, and p-S396-tau could be effective in diagnosing AD as blood biomarkers, despite the limitation in the meta-analysis based on the availability of data. Therefore, certain BDE proteins could be used as effective biomarkers for AD.

scholarly journals Astrocytic transporters in Alzheimer's disease

2017 ◽  
Vol 474 (3) ◽  
pp. 333-355 ◽  
Author(s):  
Chris Ugbode ◽  
Yuhan Hu ◽  
Benjamin Whalley ◽  
Chris Peers ◽  
Marcus Rattray ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Neurological Diseases ◽  
Current Evidence ◽  
Specific Targeting ◽  
Disease Modifying Therapies ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
And Function

Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both cellular and molecular changes at an early stage in neurological diseases, including Alzheimer's disease (AD). These changes may reflect a change from a neuroprotective to a neurotoxic phenotype. Given the lack of current disease-modifying therapies for AD, astrocytes have become an interesting and viable target for therapeutic intervention. The astrocyte transport system covers a diverse array of proteins involved in metabolic support, neurotransmission and synaptic architecture. Therefore, specific targeting of individual transporter families has the potential to suppress neurodegeneration, a characteristic hallmark of AD. A small number of the 400 transporter superfamilies are expressed in astrocytes, with evidence highlighting a fraction of these are implicated in AD. Here, we review the current evidence for six astrocytic transporter subfamilies involved in AD, as reported in both animal and human studies. This review confirms that astrocytes are indeed a viable target, highlights the complexities of studying astrocytes and provides future directives to exploit the potential of astrocytes in tackling AD.

scholarly journals Functions of the Alzheimer’s Disease Protease BACE1 at the Synapse in the Central Nervous System

2016 ◽  
Vol 60 (3) ◽  
pp. 305-315 ◽  
Author(s):  
Kathryn M. Munro ◽  
Amelia Nash ◽  
Martina Pigoni ◽  
Stefan F. Lichtenthaler ◽  
Jenny M. Gunnersen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Central Nervous System ◽  
Nervous System ◽  
The Central Nervous System

scholarly journals The Innate Immune System in Alzheimer’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Allal Boutajangout ◽  
Thomas Wisniewski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Innate Immune System ◽  
Late Onset ◽  
Innate Immune ◽  
Amyloid Angiopathy ◽  
Functional Variant ◽  
The Central Nervous System ◽  
Congophilic Amyloid Angiopathy

Alzheimer’s disease (AD) is the leading cause for dementia in the world. It is characterized by two biochemically distinct types of protein aggregates: amyloidβ(Aβ) peptide in the forms of parenchymal amyloid plaques and congophilic amyloid angiopathy (CAA) and aggregated tau protein in the form of intraneuronal neurofibrillary tangles (NFT). Several risk factors have been discovered that are associated with AD. The most well-known genetic risk factor for late-onset AD is apolipoprotein E4 (ApoE4) (Potter and Wisniewski (2012), and Verghese et al. (2011)). Recently, it has been reported by two groups independently that a rare functional variant (R47H) of TREM2 is associated with the late-onset risk of AD. TREM2 is expressed on myeloid cells including microglia, macrophages, and dendritic cells, as well as osteoclasts. Microglia are a major part of the innate immune system in the CNS and are also involved in stimulating adaptive immunity. Microglia express several Toll-like receptors (TLRs) and are the resident macrophages of the central nervous system (CNS). In this review, we will focus on the recent advances regarding the role of TREM2, as well as the effects of TLRs 4 and 9 on AD.

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