Pregledni rad
The role of the LRP1 receptor in the draining of amyloid beta (Aβ) peptide across the blood brain barrier (BBB)
Nikola Barić
Sažetak
A number of recent investigations about the etiology and patophysiology of Alzheimer’s disease (AD) emphasize the importance of the intra-arterial perivascular drainage (IPAD) of the amyloid beta (Aβ) from the brain, including the drainage from the blood brain barrier (BBB). They also emphasize the crucial factor in these events, the huge transmembrane low-density lipoprotein receptor-related protein 1 (LRP1). By binding within the BBB capillary wall basement membrane with the specific LRP1 ligand binding domains, Aβ induces a number of mechanical and biochemical events that are essential for the activation of the PICALM/clathrin-dependent endocytosis, transcytosis, and exocytosis, the crucial factors for adequate Aβ drainage from the brain. This drainage is otherwise immesurably im- portant for the proper Aβ homeostasis, because its impairment has a vital role in the pathophysiology and destructive effects of AD. It is evident that the altered Aβ homeostasis induces Aβ elevated aggre- gation and deposition which are the basis of the disease. A number of recent investigations emphasize that the binding of Aβ induces specific conformational changes in the extracellular and intracellular receptor structures. Extracellular conformational changes of the receptor structure are reflected in the structure of the receptor intracellular tail, with the binding of PICALM protein to the YXXL motif
of the tail and with the consequent recruitment of a number of signal proteins, as well as in the onset of PICALM/clathrin-dependent Aβ endocytosis, transcytosis and exocytosis into the capillary circula- tion. However, a profound insight into the available literature related to these events does not give a satisfactory explanation of these events. Consequently, this study is concerned with the problem of Aβ binding to LRP1, and with local conformational changes on the receptor tail which are activators of Aβ endocytosis, transcytosis, and its exocytosis into the capillary blood. This study, in fact, presents the author’s hypothetical approach to the problem, with the aim to contribute to the better understanding of AD.
Ključne riječi
Alzheimer’s disease pathophysiology; low-density lipoprotein receptor-related protein 1 (LRP1); intra-arterial perivascular Aβ drainage; PICALM; YXXL motif; endocytosis; transcytosis;
Hrčak ID:
269888
URI
Datum izdavanja:
27.12.2021.
Posjeta: 554 *