TY - JOUR
T1 - Neuroprotein Targets of γ-Diketone Metabolites of Aliphatic and Aromatic Solvents That Induce Central–Peripheral Axonopathy
AU - Spencer, Peter S.
N1 - Funding Information:
The author discloses receipt of the following financial support for the research, authorship, and/or publication of this article: The toxicogenomic and proteomic studies reported here for the first time were supported by grant U19 ES011384 from the National Institute of Environmental Health Sciences.
Funding Information:
The experimental studies reviewed here were variously performed by students, technicians, postdoctoral fellows, and faculty colleagues at Albert Einstein College of Medicine, Oregon Health & Science University, Oregon State University, Pacific Northwest National Laboratory, and University of Houston; in surname alphabetical order: Joshua Adkins (proteomics), Monica Bischoff (animal studies), Alan Cranson (toxicogenomics), Max Deinzer (mass spectrometry), David Dixon (computation), Dickran Houropian (neuropathology), Seyed Hashemi (protein studies), Robert Kayton (electron microscopy), Min-Sun Kim (neuropathology), Michael Lasarev (biostatistics), Valerie Palmer (animal studies and toxicogenomics), the late Edith Peterson (tissue culture), Michael Politis (animal studies), Colin Poole (chromatography), Joel Pounds (proteomics), Mohammad Sabri (protein studies), Herbert Schaumburg (neurology and neuropathology), Mary Seelig (tissue culture), Dean Sproles (toxicogenomics), Arnold Sterman (neuropathology), Sarah Trimpkin (mass spectrometry), Desire Tshala-Katumbay (neuropathology and protein studies), Bellina Veronesi (tissue culture), Joy Zagoren (animal studies), Chang-Guo Zhan (computation studies), and the late Albert Zlatkis (chromatography). The author thank Chen Xiao for discussion. Ann Hubbs kindly reviewed the article. The author discloses receipt of the following financial support for the research, authorship, and/or publication of this article: The toxicogenomic and proteomic studies reported here for the first time were supported by grant U19 ES011384 from the National Institute of Environmental Health Sciences.
Publisher Copyright:
© The Author(s) 2020.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Peripheral neuropathy associated with chronic occupational and deliberate overexposure to neurotoxic organic solvents results from axonal degeneration in the central and peripheral nervous system. Human and experimental studies show that axonopathy is triggered by the action of neuroprotein-reactive γ-diketone metabolites formed from exposure to certain aliphatic solvents (n-hexane, 2-hexanone) and aromatic compounds (1,2-diethylbenzene, 1,2-4-triethylbenzene, 6-acetyl-1,1,4,4-tetramethyl-7-ethyl-1,2,3,4-tetralin). Neuroprotein susceptibility is related primarily to their differential content of lysine, the ∊-amino group of which is targeted by γ-diketones. Specific neuroprotein targets have been identified, and the sequence of molecular mechanisms leading to axonal pathology has been illuminated. While occupational n-hexane neuropathy continues to be reported, lessons learned from its experimental study may have relevance to other causes of peripheral neuropathy, including those associated with aging and diabetes mellitus.
AB - Peripheral neuropathy associated with chronic occupational and deliberate overexposure to neurotoxic organic solvents results from axonal degeneration in the central and peripheral nervous system. Human and experimental studies show that axonopathy is triggered by the action of neuroprotein-reactive γ-diketone metabolites formed from exposure to certain aliphatic solvents (n-hexane, 2-hexanone) and aromatic compounds (1,2-diethylbenzene, 1,2-4-triethylbenzene, 6-acetyl-1,1,4,4-tetramethyl-7-ethyl-1,2,3,4-tetralin). Neuroprotein susceptibility is related primarily to their differential content of lysine, the ∊-amino group of which is targeted by γ-diketones. Specific neuroprotein targets have been identified, and the sequence of molecular mechanisms leading to axonal pathology has been illuminated. While occupational n-hexane neuropathy continues to be reported, lessons learned from its experimental study may have relevance to other causes of peripheral neuropathy, including those associated with aging and diabetes mellitus.
KW - 1,2-diacetylbenzene; neuropathy
KW - axonopathy
KW - diabetes mellitus
KW - lysine
KW - n-hexane
KW - neuroproteins
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U2 - 10.1177/0192623320910960
DO - 10.1177/0192623320910960
M3 - Review article
C2 - 32162603
AN - SCOPUS:85081950798
VL - 48
SP - 411
EP - 421
JO - Toxicologic Pathology
JF - Toxicologic Pathology
SN - 0192-6233
IS - 3
ER -