Related Experiment Video
Updated: Jul 11, 2026
09:00
Biochemical Purification and Proteomic Characterization of Amyloid Fibril Cores from the Brain
Published on: April 28, 2022
The FE65 proteins and Alzheimer's disease
Declan M McLoughlin1, Christopher C J Miller
1Section of Old Age Psychiatry, Institute of Psychiatry, King's College London, MRC Centre for Neurodegeneration Research, London, United Kingdom. d.mcloughlin@iop.kcl.ac.uk
Journal of Neuroscience Research
|September 11, 2007
Summary
The FE65 family of proteins interacts with amyloid precursor protein (APP) and plays a crucial role in brain development. Disrupting FE65 genes leads to neurodevelopmental defects, suggesting a role in Alzheimer's disease pathogenesis.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- FE65 proteins (FE65, FE65L1, FE65L2) are multidomain adaptors involved in protein complex formation.
- FE65 is brain-enriched, while FE65L1/L2 are widely expressed, all possessing WW and PTB domains.
- These proteins interact with the amyloid precursor protein (APP) intracellular domain (AICD), influencing APP processing and gene transcription.
Purpose of the Study:
- To review the known functions of the FE65 protein family.
- To elucidate the role of FE65 proteins in APP processing and function.
- To explore the involvement of FE65 proteins in Alzheimer's disease.
Main Methods:
- Literature review of studies on FE65 protein family.
- Analysis of protein-protein interactions involving FE65 domains (WW, PTB1, PTB2).
- Examination of knockout mouse models (single and double FE65/FE65L1) and their neurodevelopmental phenotypes.
Main Results:
- FE65 proteins bind AICD, affecting APP processing and nuclear translocation for gene transcription.
- Interactions with transcription factors (CP2, Tip60) and SET protein mediate nuclear functions.
- FE65 also interacts with LRP, ApoEr2, and Mena, influencing cytoskeleton, motility, and neuronal development.
- Double FE65/FE65L1 knockout mice exhibit severe neurodevelopmental defects, including axonal pathfinding issues.
Conclusions:
- FE65 proteins are critical for normal neurodevelopment, potentially acting in a signaling pathway with APP and Mena.
- Dysregulation of FE65 function may contribute to neurodevelopmental disorders and Alzheimer's disease.
- Further research is needed to confirm FE65 target genes and fully understand its role in disease.
Related Concept Videos
01:23Alzheimer Disease ll: Pathophysiology
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
01:26Alzheimer's Disease: Overview
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
01:29Alzheimer Disease l: Introduction
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
01:22Alzheimer's Disease: Treatment
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...