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Open AccessLimitations of the human iPSC-derived neuron model for early-onset Alzheimer’s disease
Non-familial Alzheimer’s disease (AD) occurring before 65 years of age is commonly referred to as early-onset Alzheimer’s disease (EOAD) and constitutes ~ 5–6% of all AD cases (Mendez et al. in Continuum 25:34...
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Protocol
Human-Induced Pluripotent Stem Cell (hiPSC)-Derived Neurons and Glia for the Elucidation of Pathogenic Mechanisms in Alzheimer’s Disease
Alzheimer’s disease (AD) is a common neurodegenerative disorder and a mechanistically complex disease. For the last decade, human models of AD using induced pluripotent stem cells (iPSCs) have emerged as a pow...
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Article
Amyloid-β-independent regulators of tau pathology in Alzheimer disease
The global epidemic of Alzheimer disease (AD) is worsening, and no approved treatment can revert or arrest progression of this disease. AD pathology is characterized by the accumulation of amyloid-β (Aβ) plaqu...
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Article
Chromatin establishes an immature version of neuronal protocadherin selection during the naive-to-primed conversion of pluripotent stem cells
In the mammalian genome, the clustered protocadherin (cPCDH) locus provides a paradigm for stochastic gene expression with the potential to generate a unique cPCDH combination in every neuron. Here we report a ch...
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Article
Open AccessProbing the Secrets of Alzheimer’s Disease Using Human-induced Pluripotent Stem Cell Technology
Our understanding of Alzheimer’s disease (AD) is still incomplete and, as a result, we lack effective therapies. Reprogramming to generate human-induced pluripotent stem cells provides a new approach to the ge...
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Human Stem Cell Approaches to Understanding and Treating Alzheimer’s Disease
This chapter describes how human induced pluripotent stem cell (hIPSC) technologies might be used to study Alzheimer’s disease. I argue that significant mechanistic and therapeutic insights may emerge regardin...
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Article
Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells
Induced pluripotent stem cells are shown to be useful for studying phenotypes relevant to familial and sporadic Alzheimer’s disease, even though it can take decades for the disease to manifest in patients.
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Article
Somatic coding mutations in human induced pluripotent stem cells
Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unkn...
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Article
Kinesin-mediated axonal transport of a membrane compartment containing β-secretase and presenilin-1 requires APP
Proteolytic processing of amyloid precursor protein (APP) generates amyloid-β peptide and has been implicated in the pathogenesis of Alzheimer's disease1. However, the normal function of APP, whether this functio...
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Article
ADP-induced rocking of the kinesin motor domain revealed by single-molecule fluorescence polarization microscopy
Kinesin is an ATP-driven molecular motor protein that moves processively along microtubules. Despite considerable research, the detailed mechanism of kinesin motion remains elusive. We applied an enhanced suit...
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Article
The muscle in kinesin
The first high resolution structures of the kinesin and NCD motor proteins reveal their surprising similarity to myosin but leave open the tantalizing question of what properties determine the directionality o...
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New cytoskeletal liaisons
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A brave new world for dynein
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Bead movement by single kinesin molecules studied with optical tweezers
KINESIN, a mechanoenzyme that couples ATP hydrolysis to movement along microtubules, is thought to power vesicle transport and other forms of microtubule-based motility1–6. Here, microscopic silica beads7 were pr...
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Article
Erratum: Identification of globular mechanochemical heads of kinesin
Nature 338, 355-357 (1989). AN error in Fig. 1 legend of this letter, in which MgATP was substituted for MgADP, caused the legend to be misleading. A correct explanation is: Kinesin from the Biogel column (lan...
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Article
Identification of globular mechanochemical heads of kinesin
KINESIN is a mechanoenzyme which uses energy liberated from ATP hydrolysis to transport particles towards the 'plus ends' of microtubules1–6. The enzyme consists of two polypeptide heavy chains of relative molecu...
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Article
Mechanisms of chromosome orientation revealed by two meiotic mutants in Drosophila melanogaster
Two disjunction defective meiotic mutants, ord and mei-S332, each of which disrupts meiosis in both male and female Drosophila melanogaster, were analyzed cytologically and genetically in the male germ-line. It w...