Cogitations on a proteocentric lexicon.

Neurobiology of Aging 21 (2000) 563–564 www.elsevier.com/locate/neuaging Commentary Cogitations on a proteocentric lexicon David B. Teplow* Department of Neurology (Neuroscience), Harvard Medical School, and Center for Neurologic Diseases, Brigham and Women’s Hospital, Boston, MA 02115, USA Technical terms are the currency with which the business of science is conducted. Terminology provides the means to communicate complex ideas quickly and efficiently. This capability is maximized by agreement of the scientific com- munity that a particular term means a particular thing. Terms may describe physicochemical entities, such as DNA, amino acids, or membranes; or processes, such as apoptosis, axonal transport, or mitosis. In each case, these terms incorporate many quanta of experimentally-deter- mined chemical, biochemical, structural, or physiological information. In addition, implicit in the usage of scientific terminology are intangible elements, including prevailing assumptions and dogma. For example, the term amyloid originated from the tangible observation of abnormal dep- osition of a substance in the brain and the assumption that this substance was “starch-like.” Combinations of tangible and intangible elements not only shape our definitions of scientific terms but create implicit intellectual and concep- tual boundaries for scientific discourse and experimentation. These boundaries are at the same time inclusive and exclu- sive, and where these boundaries lie has profound effects on the manner in which science is conducted. If too narrow, academic consideration of certain scientific questions may exclude possible answers and explanations. If too broad, analysis of the question may become hopelessly complex due to the sheer breadth of information with apparent rele- vance. In an accompanying article, Walker and LeVine argue, in essence, that recent new discoveries concerning the involve- ment of proteins in neurodegenerative diseases necessitate a reappraisal of the use of the term “amyloid.” Their argument appears to rest upon two important observations. First, amy- loid deposits are not composed of starch, a fact which has been known for many decades. Second, the pathobiology of a number of protein deposition diseases is not consistent with that of a typical amyloidosis, i.e., the formation and deposition of amyloid fibrils. Recent studies showing that * Tel.: ⫹617-525-5270; fax: ⫹617-525-5252. E-mail address: teplow@cnd.bwh.harvard.edu (D.B. Teplow). nonfibrillar and protofibrillar protein assemblies can be cy- totoxic support this second point [3,5]. These studies have raised the question of whether the proximate effectors of neurotoxicity in vivo are in fact soluble oligomers or pro- tofibrils, and not typical amyloid-type assemblies. For these and other reasons, Walker and LeVine suggest that a more appropriate general term to define neurodegenerative dis- eases involving aberrant protein folding, assembly, or dep- osition would be “proteopathies.” The classical amyloid- oses, associated with Congo Red binding and cross- ␤ structure, would be referred to as “ ␤ -proteopathies,” while those proteopathies associated with the brain would be the “cerebral proteopathies.” In evaluating new terminology, two questions must be addressed: 1) Is there a need for the new term? and 2) Does the definition of the new term incorporate appropriate tan- gible and intangible elements? In the case of the term “proteopathy,” it is unclear whether these questions can be answered in the affirmative. Language is malleable, and in fact, over time, the meanings of many words may change. Although some (I included) may find this objectionable and would instead prefer creation of new words, if the goal of language is to facilitate communication, then a gradual logoistic drift may not only be desirable, but essential. As discussed above, although “amyloid” clearly is a misnomer, scientists now understand well what this word means, both with respect to its implications of protein deposition within tissues and of biophysical characteristics including fibril formation, cross- ␤ structure, and Congo Red staining. In addition, the word “amyloid,” and its abbreviation “A,” are part of an accepted paradigm for the naming of amyloid proteins [4]. Thus, it is not obvious that replacing this term with “ ␤ -proteopathies” is necessary or advantageous. This could be one reason why George Glenner’s use of the term “ ␤ -fibrilloses,” even in the context of an important review article in the New England Journal of Medicine [1,2], did not subsequently result in the use of this term rather than “amyloidoses.” Even if the need for new terminology were compelling, implicit in the proposed definition of “cerebral proteopathy” are conceptual boundaries that result in the 0197-4580/00/$ – see front matter. Published by Elsevier Science Inc. All rights reserved. PII: S 0 1 9 7 - 4 5 8 0 ( 0 0 ) 0 0 1 5 9 - 7