PMID- 9185121
OWN - NLM
STAT- MEDLINE
DCOM- 19970826
LR  - 20190822
IS  - 0306-9877 (Print)
IS  - 0306-9877 (Linking)
VI  - 48
IP  - 5
DP  - 1997 May
TI  - The possible role of peroxynitrite in Alzheimer's disease: a simple hypothesis 
      that could be tested more thoroughly.
PG  - 375-80
AB  - Alzheimer's disease is characterized by the development of a degenerative 
      condition in the elderly, associated with dementia. Upon pathological 
      examination, cerebral amyloid plaques are found which contain denatured protein 
      or peptide material. The process of denaturation of protein requires the presence 
      of excessive heat, organic solvents, or oxidizing acids (OA). It seems that only 
      OA could produce these effects since the other two are not present in the 
      disease. Macrophages can produce the anion of an oxidizing acid known as 
      peroxynitrite (OONO). This material is formed from two free radical gases, namely 
      superoxide anion [.O2]- and nitric oxide (.N = O). Although (OONO)- is very 
      reactive (1000 times more oxidizing than hydrogen peroxide), its half life in 
      solution is only 1 to 2 seconds. Therefore, when it oxidizes a substance (such as 
      protein) peroxynitrite disappears. The brain contains cells called microglia 
      which are produced from monocytes in the same way as other types of macrophages 
      from the lung and liver etc. The macrophages from the lung (alveolar) and liver 
      (Kupfer cells) produce large amounts of peroxynitrite when activated by particles 
      (silica) or infectious agents (lipopolysaccharide or interferon). Microglia 
      produce highly oxidizing substances as well, but no one has ever measured 
      production of peroxynitrite from these cells. Assuming that microglia produce 
      peroxynitrite, or other similar oxidants, anti-oxidant and anti-inflammatory 
      drugs should be helpful in treatment of early forms of the disease. In addition, 
      large doses of anti-oxidant vitamin C and vitamin E might be helpful to people 
      with Alzheimer's disease.
FAU - Van Dyke, K
AU  - Van Dyke K
AD  - Department of Pharmacology & Toxicology, Robert C. Byrd Health Sciences Center, 
      West Virginia University, Morgantown 26506, USA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Med Hypotheses
JT  - Medical hypotheses
JID - 7505668
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitrates)
RN  - 26404-66-0 (peroxynitric acid)
SB  - IM
MH  - Alzheimer Disease/drug therapy/*etiology/*metabolism
MH  - Amyloid beta-Protein Precursor/chemistry/metabolism
MH  - Anti-Inflammatory Agents/therapeutic use
MH  - Antioxidants/therapeutic use
MH  - Humans
MH  - Inflammation/etiology
MH  - Microglia/metabolism
MH  - *Models, Biological
MH  - NF-kappa B/metabolism
MH  - Nitrates/*metabolism
MH  - Protein Denaturation
EDAT- 1997/05/01 00:00
MHDA- 1997/05/01 00:01
CRDT- 1997/05/01 00:00
PHST- 1997/05/01 00:00 [pubmed]
PHST- 1997/05/01 00:01 [medline]
PHST- 1997/05/01 00:00 [entrez]
AID - S0306-9877(97)90031-1 [pii]
AID - 10.1016/s0306-9877(97)90031-1 [doi]
PST - ppublish
SO  - Med Hypotheses. 1997 May;48(5):375-80. doi: 10.1016/s0306-9877(97)90031-1.