Current and future treatment of amyloid diseases

Abstract There are more than 30 human proteins whose aggregation appears to cause degenerative maladies referred to as amyloid diseases or amyloidoses. These disorders are named after the characteristic cross‐β‐sheet amyloid fibrils that accumulate systemically or are localized to specific organs. In most cases, current treatment is limited to symptomatic approaches and thus disease‐modifying therapies are needed. Alzheimer's disease is a neurodegenerative disorder with extracellular amyloid β‐peptide (Aβ) fibrils and intracellular tau neurofibrillary tangles as pathological hallmarks. Numerous clinical trials have been conducted with passive and active immunotherapy, and small molecules to inhibit Aβ formation and aggregation or to enhance Aβ clearance; so far such clinical trials have been unsuccessful. Novel strategies are therefore required and here we will discuss the possibility of utilizing the chaperone BRICHOS to prevent Aβ aggregation and toxicity. Type 2 diabetes mellitus is symptomatically treated with insulin. However, the underlying pathology is linked to the aggregation and progressive accumulation of islet amyloid polypeptide as fibrils and oligomers, which are cytotoxic. Several compounds have been shown to inhibit islet amyloid aggregation and cytotoxicity in vitro. Future animal studies and clinical trials have to be conducted to determine their efficacy in vivo. The transthyretin (TTR) amyloidoses are a group of system...
Source: Journal of Internal Medicine - Category: Internal Medicine Authors: Tags: Review Source Type: research

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
CONCLUSION: The optimal management of modifiable risk factors may be important for preventing dementia in subjects with diabetes mellitus. PMID: 31769236 [PubMed - as supplied by publisher]
Source: Diabetes and Metabolism Journal - Category: Endocrinology Tags: Diabetes Metab J Source Type: research
This study suggests that (D-Ser2)Oxm holds promise for the prevention and treatment of AD. PMID: 31765661 [PubMed - as supplied by publisher]
Source: Hormones and Behavior - Category: Endocrinology Authors: Tags: Horm Behav Source Type: research
In conclusion, AFM is a user-friendly tool that supplies multiparametric data, rendering it a most valuable technique. PMID: 31755391 [PubMed - as supplied by publisher]
Source: Current Topics in Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Top Med Chem Source Type: research
Authors: Kim YG, Park DG, Moon SY, Jeon JY, Kim HJ, Kim DJ, Lee KW, Han SJ Abstract BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk for dementia. The effects of hypoglycemia on dementia are controversial. Thus, we evaluated whether hypoglycemia increases the risk for dementia in senior patients with T2DM. METHODS: We used the Korean National Health Insurance Service Senior cohort, which includes>10% of the entire senior population of South Korea. In total, 5,966 patients who had ever experienced at least one episode of hypoglycemia were matched with those who had not, using p...
Source: Diabetes and Metabolism Journal - Category: Endocrinology Tags: Diabetes Metab J Source Type: research
Abstract BACKGROUND: There is an increasing interest on cognitive impairment (CI) in patients with type 2 diabetes mellitus (T2DM), but evidence is conflicting regarding the association between CI and glycemic control. OBJECTIVE: The present study aimed to estimate the prevalence of CI in patients with T2DM from northern rural China in order to determine whether cognitive dysfunction is related to glycemic control. METHODS: First, we conducted a study with a cross-sectional design. We performed cluster random sampling of 1848 residents who were aged 60 years or older and lived in the countryside in China...
Source: Current Alzheimer Research - Category: Neurology Authors: Tags: Curr Alzheimer Res Source Type: research
Active-site environment of Cu bound amyloid β and amylin peptides. J Biol Inorg Chem. 2019 Oct 16;: Authors: Pal I, Roy M, Dey SG Abstract Alzheimer's disease (AD) and Type 2 Diabetes mellitus (T2Dm), two of the most common amyloidogenic diseases. They share a common pathological symptom, i.e., the formation of amyloid deposits comprised of amyloid β and amylin peptides, respectively. Autopsy of brains of AD-affected patients shows the presence of abnormally high concentrations of Cu in the deposited amyloid β plaques, while a significantly higher level of Cu is found in the serum of pa...
Source: Journal of Biological Inorganic Chemistry : JBIC - Category: Chemistry Authors: Tags: J Biol Inorg Chem Source Type: research
We examined electroencephalography (EEG) correlates of cognitive function in healthy aging and 2 of the most prominent and debilitating age-related disorders: type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). Relative to healthy controls (HC), patients with AD were impaired on nearly every cognitive measure, whereas patients with T2DM performed worse mainly on learning and memory tests. A continuum of alterations in resting-state EEG was associated with pathological aging, generally characterized by reduced alpha (α) and beta (β) power (AD HC), with some variations across different brain regions. The...
Source: Neurobiology of Aging - Category: Geriatrics Authors: Tags: Neurobiol Aging Source Type: research
In conclusion, older adults exhibited decreased markers of UPR activation and reduced coordination with autophagy and SC-associated gene transcripts following a single bout of unaccustomed resistance exercise. In contrast, young adults demonstrated strong coordination between UPR genes and key regulatory gene transcripts associated with autophagy and SC differentiation in skeletal muscle post-exercise. Taken together, the present findings suggest a potential age-related impairment in the post-exercise transcriptional response that supports activation of the UPR and coordination with other exercise responsive pathways (i.e....
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Neurodegeneration in late life is a very complex phenomenon, and its complexity strains against the nice neat clinical definitions of disease found in the textbooks. Different patients with Alzheimer's disease can exhibit quite different mixes of various forms of pathology, developing at different paces and times: aggregates of amyloid-β, tau, and α-synuclein; vascular degeneration; markers of neuroinflammation; metabolic disruption similar to that of diabetes, and so forth. One case of Alzheimer's might be different enough from another to require a different designation. Thus researchers talk about defining sub...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
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