ALZHEIMERS-DISEASE - A CELL BIOLOGICAL PERSPECTIVE

被引:267
作者
KOSIK, KS [1 ]
机构
[1] BRIGHAM & WOMENS HOSP, CTR NEUROL DIS, DEPT MED, DIV NEUROL, BOSTON, MA 02115 USA
关键词
D O I
10.1126/science.1589757
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
An almost bewildering number of findings concerning Alzheimer's disease mask the significant recent progress in understanding the molecular basis of some inherited forms of this disease and the proteolytic processing of proteins related to the disease. Alzheimer's disease is an amyloidosis, a condition in which certain proteins or protein fragments precipitate in various tissues as amyloid, fibrillar aggregates with a beta-pleated sheet conformation. Alzheimer's is also characterized by neuritic lesions and cell death. Some rare forms of the disease are now known to arise from a mutation in an amyloidogenic protein. Another recent insight is the discovery of an endosomal-lysosomal processing pathway capable of generating protein fragments that can deposit extracellularly as amyloid fibrils. Key future directions for cellular-based research in Alzheimer's disease include the study of membrane trafficking and the passage of intracellular material to the extracellular milieu, molecular signaling among intracellular compartments, the interaction between organelles and the neuronal cytoskeleton, and the nature of cytoskeletal reorganization after neuronal injury.
引用
收藏
页码:780 / 783
页数:4
相关论文
共 121 条
[41]   ISOLATION AND PARTIAL CHARACTERIZATION OF NEUROFIBRILLARY TANGLES AND AMYLOID PLAQUE CORE IN ALZHEIMERS-DISEASE - IMMUNOHISTOLOGICAL STUDIES [J].
GOREVIC, PD ;
GONI, F ;
PONSESTEL, B ;
ALVAREZ, F ;
PERESS, NS ;
FRANGIONE, B .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1986, 45 (06) :647-664
[42]  
GREENBERG SG, 1992, J BIOL CHEM, V267, P564
[43]   A PREPARATION OF ALZHEIMER PAIRED HELICAL FILAMENTS THAT DISPLAYS DISTINCT TAU-PROTEINS BY POLYACRYLAMIDE-GEL ELECTROPHORESIS [J].
GREENBERG, SG ;
DAVIES, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (15) :5827-5831
[44]  
GRUNDKEIQBAL I, 1986, J BIOL CHEM, V261, P6084
[45]  
HAASS C, 1991, J NEUROSCI, V11, P3783
[46]  
HAASS C, IN PRESS NATURE
[47]   MICROTUBULE DESTABILIZATION AND NEUROFILAMENT PHOSPHORYLATION PRECEDE DENDRITIC SPROUTING AFTER CLOSE AXOTOMY OF LAMPREY CENTRAL NEURONS [J].
HALL, GF ;
LEE, VMY ;
KOSIK, KS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (11) :5016-5020
[48]  
HARDY J, 1991, LANCET, V337, P1342
[49]   AGGREGATION AND SECONDARY STRUCTURE OF SYNTHETIC AMYLOID BETA-A4 PEPTIDES OF ALZHEIMERS-DISEASE [J].
HILBICH, C ;
KISTERSWOIKE, B ;
REED, J ;
MASTERS, CL ;
BEYREUTHER, K .
JOURNAL OF MOLECULAR BIOLOGY, 1991, 218 (01) :149-163
[50]   STRUCTURE OF THE BOVINE TAU-GENE - ALTERNATIVELY SPLICED TRANSCRIPTS GENERATE A PROTEIN FAMILY [J].
HIMMLER, A .
MOLECULAR AND CELLULAR BIOLOGY, 1989, 9 (04) :1389-1396