scholarly journals Understanding PDE4's function in Alzheimer's disease; a target for novel therapeutic approaches

2019 ◽  
Vol 47 (5) ◽  
pp. 1557-1565 ◽  
Author(s):  
Amy J. Tibbo ◽  
Gonzalo S. Tejeda ◽  
George S. Baillie
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Camp Response Element Binding ◽  
Cellular Tissue ◽  
Therapeutic Approaches ◽  
Camp Response Element ◽  
Age Related ◽  
Expression Activity ◽  
Activation Status

Abstract Phosphodiesterases (PDEs) have long been considered as targets for the treatment of Alzheimer's disease (AD) and a substantial body of evidence suggests that one sub-family from the super-family of PDEs, namely PDE4D, has particular significance in this context. This review discusses the role of PDE4 in the orchestration of cAMP response element binding signaling in AD and outlines the benefits of targeting PDE4D specifically. We examine the limited available literature that suggests PDE4 expression does not change in AD brains together with reports that show PDE4 inhibition as an effective treatment in this age-related neurodegenerative disease. Actually, aging induces changes in PDE4 expression/activity in an isoform and brain-region specific manner that proposes a similar complexity in AD brains. Therefore, a more detailed account of AD-related alterations in cellular/tissue location and the activation status of PDE4 is required before novel therapies can be developed to target cAMP signaling in this disease.

scholarly journals Overview of Alzheimer’s Disease and Some Therapeutic Approaches Targeting Aβby Using Several Synthetic and Herbal Compounds

2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Sandeep Kumar Singh ◽  
Saurabh Srivastav ◽  
Amarish Kumar Yadav ◽  
Saripella Srikrishna ◽  
George Perry
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Neurodegenerative Disease ◽  
Therapeutic Approaches ◽  
Age Related

Alzheimer’s disease (AD) is a complex age-related neurodegenerative disease. In this review, we carefully detail amyloid-βmetabolism and its role in AD. We also consider the various genetic animal models used to evaluate therapeutics. Finally, we consider the role of synthetic and plant-based compounds in therapeutics.

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   

scholarly journals Inverse Correlation Between Alzheimer’s Disease and Cancer: Short Overview

2021 ◽  
Author(s):  
Agnieszka Zabłocka ◽  
Wioletta Kazana ◽  
Marta Sochocka ◽  
Bartłomiej Stańczykiewicz ◽  
Maria Janusz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Kinase Inhibitor ◽  
Fungal Infections ◽  
Neurological Diseases ◽  
Inverse Correlation ◽  
Biological Mechanisms ◽  
Age Related ◽  
Common Risk Factors

AbstractThe negative association between Alzheimer’s disease (AD) and cancer suggests that susceptibility to one disease may protect against the other. When biological mechanisms of AD and cancer and relationship between them are understood, the unsolved problem of both diseases which still touches the growing human population could be overcome. Actual information about biological mechanisms and common risk factors such as chronic inflammation, age-related metabolic deregulation, and family history is presented here. Common signaling pathways, e.g., p53, Wnt, role of Pin1, and microRNA, are discussed as well. Much attention is also paid to the potential impact of chronic viral, bacterial, and fungal infections that are responsible for the inflammatory pathway in AD and also play a key role to cancer development. New data about common mechanisms in etiopathology of cancer and neurological diseases suggests new therapeutic strategies. Among them, the use of nilotinib, tyrosine kinase inhibitor, protein kinase C, and bexarotene is the most promising.

scholarly journals Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects?

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 968 ◽  
Author(s):  
Sunitha Kodidela ◽  
Kelli Gerth ◽  
Sanjana Haque ◽  
Yuqing Gong ◽  
Saifudeen Ismael ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Extracellular Vesicles ◽  
Treatment Strategies ◽  
Progressive Dementia ◽  
Hiv Patients ◽  
Age Related ◽  
Infected Cells ◽  
New Treatment

The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HAND). Various mechanisms such as neuroinflammation induced by HIV proteins (e.g., Tat, gp120, Nef), excitotoxicity, oxidative stress, and the use of ART contribute to the deposition of Aβ, leading to dementia. However, progressive dementia in older subjects with HIV might be due to HAND, AD, or both. Recently, extracellular vesicles (EVs)/exosomes, have gained recognition for their importance in understanding the pathology of both HAND and AD. EVs can serve as a possible link between HIV and AD, due to their ability to package and transport the toxic proteins implicated in both AD and HIV (Aβ/tau and gp120/tat, respectively). Given that Aß is also elevated in neuron-derived exosomes isolated from the plasma of HIV patients, it is reasonable to suggest that neuron-to-neuron exosomal transport of Aβ and tau also contributes to AD-like pathology in HIV-infected subjects. Therefore, exploring exosomal contents is likely to help distinguish HAND from AD. However, future prospective clinical studies need to be conducted to compare the exosomal contents in the plasma of HIV subjects with and without HAND as well as those with and without AD. This would help to find new markers and develop new treatment strategies to treat AD in HIV-positive subjects. This review presents comprehensive literatures on the mechanisms contributing to Aβ deposition in HIV-infected cells, the role of EVs in the propagation of Aβ in AD, the possible role of EVs in HIV-induced AD-like pathology, and finally, possible therapeutic targets or molecules to treat HIV subjects with AD.

scholarly journals Zinc-mediated Neurotransmission in Alzheimer's Disease: A Potential Role of the GPR39 in Dementia

2019 ◽  
Vol 18 (1) ◽  
pp. 2-13
Author(s):  
Michal Rychlik ◽  
Katarzyna Mlyniec
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Neural Plasticity ◽  
Modern Society ◽  
Neuroprotective Drugs ◽  
Age Related ◽  
Candidate Drug ◽  
G Protein Coupled

: With more people reaching an advanced age in modern society, there is a growing need for strategies to slow down age-related neuropathology and loss of cognitive functions, which are a hallmark of Alzheimer's disease. Neuroprotective drugs and candidate drug compounds target one or more processes involved in the neurodegenerative cascade, such as excitotoxicity, oxidative stress, misfolded protein aggregation and/or ion dyshomeostasis. A growing body of research shows that a G-protein coupled zinc (Zn2+) receptor (GPR39) can modulate the abovementioned processes. : Zn2+itself has a diverse activity profile at the synapse, and by binding to numerous receptors, it plays an important role in neurotransmission. However, Zn2+ is also necessary for the formation of toxic oligomeric forms of amyloid beta, which underlie the pathology of Alzheimer’s disease. Furthermore, the binding of Zn2+ by amyloid beta causes a disruption of zincergic signaling, and recent studies point to GPR39 and its intracellular targets being affected by amyloid pathology. : In this review, we present neurobiological findings related to Zn2+ and GPR39, focusing on its signaling pathways, neural plasticity, interactions with other neurotransmission systems, as well as on the effects of pathophysiological changes observed in Alzheimer's disease on GPR39 function. : Direct targeting of the GPR39 might be a promising strategy for the pharmacotherapy of zincergic dyshomeostasis observed in Alzheimer’s disease. The information presented in this article will hopefully fuel further research into the role of GPR39 in neurodegeneration and help in identifying novel therapeutic targets for dementia.

scholarly journals Microglia in Alzheimer’s Disease: A Target for Therapeutic Intervention

2021 ◽  
Vol 15 ◽  
Author(s):  
Guimei Zhang ◽  
Zicheng Wang ◽  
Huiling Hu ◽  
Meng Zhao ◽  
Li Sun
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Interventions ◽  
Tau Pathology ◽  
Age Related ◽  
Amyloid Accumulation ◽  
Pathophysiological Role ◽  
Inflammatory Drugs ◽  
Β Amyloid

Alzheimer’s disease (AD) is one of the most common types of age-related dementia worldwide. In addition to extracellular amyloid plaques and intracellular neurofibrillary tangles, dysregulated microglia also play deleterious roles in the AD pathogenesis. Numerous studies have demonstrated that unbridled microglial activity induces a chronic neuroinflammatory environment, promotes β-amyloid accumulation and tau pathology, and impairs microglia-associated mitophagy. Thus, targeting microglia may pave the way for new therapeutic interventions. This review provides a thorough overview of the pathophysiological role of the microglia in AD and illustrates the potential avenues for microglia-targeted therapies, including microglial modification, immunoreceptors, and anti-inflammatory drugs.

scholarly journals The role of impairment of higher mental functions in suicidogenesis in the dementia caused by Alzheimer's disease

2018 ◽  
Vol 3 (3) ◽  
pp. e0303104
Author(s):  
Iryna Mudrenko
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Risk ◽  
Suicidal Behavior ◽  
Control Group ◽  
Elderly Age ◽  
Mental Functions ◽  
Age Related ◽  
Higher Mental Functions

Background Dementia is the age-related disease. At the same time, the elderly age has one of the peaks in the number of suicides. Psychology of patients with demetia is characterized by the feeling of hopelessness, pessimism, awareness of own insolvency, dependence on others, that affects the risk of suicide. It is established that the highest risk of suicide in the early stages of dementia with the progression of cognitive deficit, the risk of suicide decreases. Aim To study the role of impairment of higher mental functions (perception, reasoning, attention, memory, emotions, will, speech) in the formation of suicidal behaviour in patients with dementia in Alzheimer's disease. Materials and methods There were examined 75 patients with dementia in Alzheimer's disease, 36 patients with a history of suicidal behavior composed the main group, and 39 patients without the signs of suicidal behavior composed control group. The study was carried out using clinical-anamnestic, psychopathological methods and mathematical statistical methods. Results The high risk of suicide in dementia caused by Alzheimer's disease is combined with the inhibition of thinking, the delusional ideas of self-blame and self-effacement (p ≤ 0.05); depressed mood, inner agitation, anxiety, feeling of despair, hopelessness, guilt, melancholia, apathy (p ≤ 0.05); effector-volitional disorders in the form of hypobulia, hypokinesia, hypomimia, decreased libido (p ≤ 0.05); speech disturbance in the form of bradylalia p ≤ 0.05; greater exhaustion and decreased attention (p ≤ 0.05). On the contrary, the following peculiarities of higher mental functions, namely thought disorder are referred to the anti-risk factors of suicide in dementia caused by Alzheimer's disease: the delusional ideas of relation and damage (p ≤ 0.05); emotions: the feeling of fear (p ≤ 0.05); effector-volitional sphere: parabulia and hyperkinesia (p ≤ 0.05). Conclusion On the basis of clinical and psychopathological study of patients with dementia in Alzheimer's disease, the specific impairment of higher mental functions and emotional-volitional spheres reasoning, memory, attention, perception, speech, emotions) are identified associated with high risk of suicide.

scholarly journals Revisiting Apathy in Alzheimer’s Disease: From Conceptualization to Therapeutic Approaches

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Antonio L. Teixeira ◽  
Mitzi M. Gonzales ◽  
Leonardo Cruz de Souza ◽  
Sara L. Weisenbach
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Activity ◽  
Prognostic Indicator ◽  
Therapeutic Approaches ◽  
Neural Basis ◽  
High Quality Evidence ◽  
Personalized Approach ◽  
Quality Evidence

Apathy is a neurobehavioral syndrome characterized by impaired motivation for goal-directed behaviors and cognitive activity, alongside blunted affect. Apathy is a common neuropsychiatric syndrome in Alzheimer’s disease (AD), with a 5-year prevalence over 70%. Apathy also serves as a prognostic indicator, correlating with the progression of AD. Despite advances in its conceptualization and understanding of its neural basis, there is very limited empirical evidence to support the available strategies for the treatment of apathy in AD. Given its complex pathophysiology, including distinct substrates for different apathy dimensions (affective, cognitive, and behavioral), it is unlikely that a single pharmacological or nonpharmacological strategy will be effective for all cases of apathy in AD. High-quality evidence research is needed to better understand the role of specific strategies aiming at a personalized approach.

Sign in / Sign up

Export Citation Format

Share Document