Insights from Drosophila models of Alzheimer's disease

2010 ◽  
Vol 38 (4) ◽  
pp. 988-992 ◽  
Author(s):  
Catherine M. Cowan ◽  
David Shepherd ◽  
Amritpal Mudher
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Protein Tau ◽  
Neurodegenerative Process ◽  
Abnormal Hyperphosphorylation ◽  
Ad Alzheimer’S Disease ◽  
The Relationship ◽  
Shed Light ◽  
Drosophila Models

AD (Alzheimer's disease) is a neurodegenerative disorder characterized by the abnormal hyperphosphorylation and aggregation of the microtubule-associated protein tau and the misfolding and deposition of Aβ peptide. The mechanisms by which tau and Aβ become abnormal is not clearly understood, neither is it known what role either protein plays in the neurodegenerative process underlying AD. We have modelled aspects of AD in Drosophila melanogaster to shed light on these processes and to further our understanding of the relationship between tau and amyloid in this disease.

scholarly journals From hybrids to new scaffolds: the latest medicinal chemistry goals in multi-target directed ligands for Alzheimer’s disease

2020 ◽  
Vol 18 ◽  
Author(s):  
Jazmín Alarcón-Espósito ◽  
Michael Mallea ◽  
Julio Rodríguez-Lavado
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Mental Deterioration ◽  
Common Causes ◽  
Β Amyloid ◽  
The One ◽  
And Function ◽  
Shed Light ◽  
Multitarget Therapy

: Alzheimer’s disease (AD) is a chronic, progressive, and fatal neurodegenerative disorder affecting cognition, behavior, and function, being one of the most common causes of mental deterioration in elderly people. Once thought as being just developed because of β amyloid depositions or neurofibrillary Tau tangles, during the last decades, numerous ADrelated targets have been established, the multifactorial nature of AD became evident. In this context, the one drug-one target paradigm has resulted to be inefficient in facing AD and other disorders with complex etiology, opening the field for the emergence of the multitarget approach. In this review, we highlight the recent advances within this area, emphasizing in hybridization tools of well-known chemical scaffolds endowed with pharmacological properties concerning AD, such as curcumin-, resveratrol-, chromone- and indole-. We focus mainly on well stablished and incipient AD therapeutic targets, AChE, BuChE, MAOs, β-amyloid deposition, 5-HT4 and Serotonin transporter, with the aim to shed light about new insights in the AD multitarget therapy.

scholarly journals Diabetes mellitus and Alzheimer’s disease

2011 ◽  
Vol 152 (13) ◽  
pp. 512-515
Author(s):  
Pál Salacz ◽  
Éva Csibri
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Effects ◽  
Neurodegenerative Process ◽  
Treatment Of Diabetes ◽  
Aging Societies ◽  
The Relationship ◽  
Positive Effect

The incidence of Alzheimer’s disease and diabetes is increasing with age. Thus, in light of demographic change and aging societies, they are becoming a growing issue for public health. Further, there are linkages between the two diseases. In particular, risk assessment studies suggest that type 2 diabetes mellitus is a risk factor of Alzheimer’s disease. Hence, even though Alzheimer’s disease can only be influenced to a limited extent, optimal treatment of diabetes mellitus may have also a positive effect on Alzheimer’s disease. While the relationship between the two diseases is not yet completely clear, in addition to the known vascular effects of diabetes mellitus recent results shed light on central nervous system effects directly influencing the neurodegenerative process. Treatment of central insulin resistance, a phenomenon explored in recent years, may be a promising avenue, not only in addressing metabolic disorder, but also Alzheimer’s disease. Orv. Hetil., 2011, 152, 512–515.

scholarly journals Neuroinflammation in Alzheimer’s Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 524
Author(s):  
Isaac G. Onyango ◽  
Gretsen V. Jauregui ◽  
Mária Čarná ◽  
James P. Bennett ◽  
Gorazd B. Stokin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Defense Mechanisms ◽  
Low Grade ◽  
Neurodegenerative Process ◽  
The Central Nervous System ◽  
Peripheral Immune Cells ◽  
The Relationship ◽  
The Brain ◽  
Gut Microbiota Dysbiosis

Alzheimer’s disease (AD) is a neurodegenerative disease associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise with increasing age. There are currently no effective disease modifying treatments for AD, resulting in increasingly large socioeconomic and personal costs. Increasing age is associated with an increase in low-grade chronic inflammation (inflammaging) that may contribute to the neurodegenerative process in AD. Although the exact mechanisms remain unclear, aberrant elevation of reactive oxygen and nitrogen species (RONS) levels from several endogenous and exogenous processes in the brain may not only affect cell signaling, but also trigger cellular senescence, inflammation, and pyroptosis. Moreover, a compromised immune privilege of the brain that allows the infiltration of peripheral immune cells and infectious agents may play a role. Additionally, meta-inflammation as well as gut microbiota dysbiosis may drive the neuroinflammatory process. Considering that inflammatory/immune pathways are dysregulated in parallel with cognitive dysfunction in AD, elucidating the relationship between the central nervous system and the immune system may facilitate the development of a safe and effective therapy for AD. We discuss some current ideas on processes in inflammaging that appear to drive the neurodegenerative process in AD and summarize details on a few immunomodulatory strategies being developed to selectively target the detrimental aspects of neuroinflammation without affecting defense mechanisms against pathogens and tissue damage.

scholarly journals Nutraceutical and Probiotic Approaches to Examine Molecular Interactions of the Amyloid Precursor Protein APP in Drosophila Models of Alzheimer’s Disease

2021 ◽  
Vol 22 (13) ◽  
pp. 7022
Author(s):  
David Jalali ◽  
Justine Anne Guevarra ◽  
Luz Martinez ◽  
Lily Hung ◽  
Fernando J Vonhoff
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Amyloid Precursor Protein ◽  
Senile Plaques ◽  
Precursor Protein ◽  
Mammalian Brain ◽  
Shed Light ◽  
Drosophila Models

Studies using animal models have shed light into the molecular and cellular basis for the neuropathology observed in patients with Alzheimer’s disease (AD). In particular, the role of the amyloid precursor protein (APP) plays a crucial role in the formation of senile plaques and aging-dependent degeneration. Here, we focus our review on recent findings using the Drosophila AD model to expand our understanding of APP molecular function and interactions, including insights gained from the fly homolog APP-like (APPL). Finally, as there is still no cure for AD, we review some approaches that have shown promising results in ameliorating AD-associated phenotypes, with special attention on the use of nutraceuticals and their molecular effects, as well as interactions with the gut microbiome. Overall, the phenomena described here are of fundamental significance for understanding network development and degeneration. Given the highly conserved nature of fundamental signaling pathways, the insight gained from animal models such as Drosophila melanogaster will likely advance the understanding of the mammalian brain, and thus be relevant to human health.

scholarly journals Alzheimer’s disease as a syndrome of overloaded amyloidic synaptic tagging in memory networks

2021 ◽  
Author(s):  
Niall Murphy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Expectancy ◽  
Amyloid Beta ◽  
Memory Loss ◽  
Phosphorylated Tau ◽  
Disease Research ◽  
Neurodegenerative Process ◽  
The Relationship ◽  
The Brain

Alzheimer’s Disease is defined as progressive memory loss coincident with accumulation of aggregated amyloid beta and phosphorylated tau. Identifying the relationship between these features has guided Alzheimer’s Disease research for decades, principally with the view that aggregated proteins drive a neurodegenerative process. Here I propose that amyloid beta and phospho-tau write-protect and tag neuroplastic changes as they form, protecting and insuring established neuroplasticity from corruption. In way of illustration, binding of oligomeric amyloid beta to the prion receptor is presented as an example possible mechanism. The write-protecting process is conjected to occur at least partially under the governance of isodendritic neuromodulators such as norepinephrine and acetylcholine. Coincident with aging, animals are exposed to accumulating amounts of memorable information. Compounded with recent increases in life expectancy and exposure to information-rich environments this causes aggregating proteins to reach unforeseen toxic levels as mnemonic circuits overload. As the brain cannot purposefully delete memories nor protect against overaccumulation of aggregating proteins, the result is catastrophic breakdown on cellular and network levels causing memory loss.

scholarly journals TREM2 Mediates Microglial Anti-Inflammatory Activations in Alzheimer’s Disease: Lessons Learned from Transcriptomics

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 321
Author(s):  
Feng Xue ◽  
Heng Du
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Critical Role ◽  
Lessons Learned ◽  
Immunoglobulin Superfamily ◽  
Missense Mutations ◽  
Anti Inflammatory ◽  
Ad Mouse Model ◽  
Shed Light

Alzheimer’s disease (AD) is a lethal neurodegenerative disorder primarily affecting the aged population. The etiopathogenesis of AD, especially that of the sporadic type, remains elusive. The triggering receptor expressed on myeloid cells 2 (TREM2), a member of TREM immunoglobulin superfamily, plays a critical role in microglial physiology. Missense mutations in human TREM2 are determined as genetic risk factors associated with the development of sporadic AD. However, the roles of TREM2 in the pathogenesis of AD are still to be established. In this review, we outlined the influence of Trem2 on balance of pro- and anti-inflammatory microglial activations from a perspective of AD mouse model transcriptomics. On this basis, we further speculated the roles of TREM2 in different stages of AD, which may shed light to the development of TREM2-targeted strategy for the prevention and treatment of this neurodegenerative disorder.

THE TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS-2 (TREM-2) AS EXPRESSION OF THE RELATIONSHIP BETWEEN MICROGLIA AND ALZHEIMER’S DISEASE: A NOVEL MARKER FOR A PROMISING PATHWAY TO EXPLORE

2018 ◽  
pp. 1-3
Author(s):  
C. Gussago ◽  
M. Casati ◽  
E. Ferri ◽  
B. Arosio
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Variants ◽  
Neurodegenerative Disorder ◽  
Myeloid Cells ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
A Cell ◽  
The Relationship ◽  
Common Neurodegenerative Disorder

Alzheimer’s disease (AD) is a common neurodegenerative disorder, strongly related with age. It has been reported that genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2), a cell-surface receptor expressed in microglial cells, greatly increase the risk of AD, thus suggesting an involvement of the microglia in the AD pathogenesis. The aim of this report is to provide an overview of the TREM2 and of its possible implication in the pathogenesis of AD.

The relationship between subcortical tau pathology and Alzheimer's disease

2012 ◽  
Vol 40 (4) ◽  
pp. 711-715 ◽  
Author(s):  
Johannes Attems ◽  
Dietmar R. Thal ◽  
Kurt A. Jellinger
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Neuronal Damage ◽  
The Other ◽  
Tau Pathology ◽  
Subcortical Nuclei ◽  
Ad Alzheimer’S Disease ◽  
The Relationship ◽  
Transentorhinal Region

The stepwise progression of tau pathology [NFTs (neurofibrillary tangles) and NTs (neuropil threads)] in AD (Alzheimer's disease) is generally assumed to begin in the transentorhinal region (entorhinal stage) from which it progresses to the hippocampus (limbic stage) and to neocortical regions (neocortical stage). This stepwise progression is reflected in the NFT Braak stages. However, it has been shown recently that tau pathology is frequently seen in subcortical nuclei, in particular the LC (locus coeruleus) in over 90% of individuals under 30 years of age, suggesting that AD-associated tau pathology begins in the LC and not in the transentorhinal region. On the other hand, only minimal amounts of tau pathology are seen in the LC in cases with considerable entorhinal tau pathology, while the severity of tau pathology in the LC significantly increases with increasing NFT Braak stages. These findings suggest that the LC becomes increasingly involved during AD progression rather than representing the site initially affected. Further studies are warranted to answer the question of whether tau pathology in the LC of young individuals is associated with AD or whether it rather reflects non-specific neuronal damage.

Auditory Dysfunction in Alzheimer's Disease

2010 ◽  
Vol 15 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Sridhar Krishnamurti
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Health Care ◽  
Care Setting ◽  
Neurodegenerative Disorder ◽  
Disease Process ◽  
Clinical Protocols ◽  
Speech Language Pathologist ◽  
Auditory Dysfunction

Alzheimer's disease is neurodegenerative disorder which affects a growing number of older adults every year. With an understanding of auditory dysfunction in Alzheimer's disease, the speech-language pathologist working in the health care setting can provide better service to these individuals. The pathophysiology of the disease process in Alzheimer's disease increases the likelihood of specific types of auditory deficits as opposed to others. This article will discuss the auditory deficits in Alzheimer's disease, their implications, and the value of clinical protocols for individuals with this disease.

Polymorphisms in the microtubuli associated protein tau and Alzheimer’s disease

2004 ◽  
Vol 36 (05) ◽  
Author(s):  
L Weller ◽  
F Faltraco ◽  
E Heimberg ◽  
S Teipel ◽  
B Bondy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Tau
Sign in / Sign up

Export Citation Format

Share Document