Alzheimer's disease is characterized by neurofibrillary tangles, senile
plaques, and neuronal death. The neurofibrillary tangles contain paired
helical filaments composed of hyperphosphorylated tau, while the senile
plaques are comprised of an array of proteins deposited around a core of
insoluble A(3 peptide).
The cause of neuronal death remains unknown, but considerable evidence suggests that it is secondary to an increase in the brain A(3 load. It has been known for nearly 10 years that the A|3 peptides are rapidly released from cells (Haass et al., 1992; Seubert et al., 1992; Shoji et al., 1992; Busciglio, Gabuzda, Matsudaira, & Yankner, 1993), but the hydrophobic amino acids at the COOH-terminus make it likely that the peptide will remain associated with the membrane following y-secretase cleavage. Thus, we hypothesized that an active process was required in order for A(3 to detach from the membrane. Selected members of the ATP-binding cassette (ABC) superfamily of transporters are responsible for the energydependent efflux of a variety of lipophilic and amphipathic molecules from cells, and the process bears a striking similarity to that which occurs with the AP peptide.
ABC transporter known as MDR1 is an Ap efflux pump.
We have identified a single ABC transporter, MDR1, as an AP efflux pump. Cells throughout the body constitutively produce and release Ap, yet the MDR1 protein is only expressed in a limited number of tissues, and is essentially undetectable in neurons
The cause of neuronal death remains unknown, but considerable evidence suggests that it is secondary to an increase in the brain A(3 load. It has been known for nearly 10 years that the A|3 peptides are rapidly released from cells (Haass et al., 1992; Seubert et al., 1992; Shoji et al., 1992; Busciglio, Gabuzda, Matsudaira, & Yankner, 1993), but the hydrophobic amino acids at the COOH-terminus make it likely that the peptide will remain associated with the membrane following y-secretase cleavage. Thus, we hypothesized that an active process was required in order for A(3 to detach from the membrane. Selected members of the ATP-binding cassette (ABC) superfamily of transporters are responsible for the energydependent efflux of a variety of lipophilic and amphipathic molecules from cells, and the process bears a striking similarity to that which occurs with the AP peptide.
ABC transporter known as MDR1 is an Ap efflux pump.
We have identified a single ABC transporter, MDR1, as an AP efflux pump. Cells throughout the body constitutively produce and release Ap, yet the MDR1 protein is only expressed in a limited number of tissues, and is essentially undetectable in neurons
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