Review Volume 13, Issue 7 pp 10770—10795

Alzheimer’s disease as a chronic maladaptive polyamine stress response

Schematic representation of the polyamine metabolism pathways in AD brain. Arginine is the mutual substrate for arginase (ARG), arginine decarboxylase (ADC), and nitric oxide synthase (NOS). Ornithine decarboxylase (ODC) decarboxylases ornithine to produce putrescine. Spermidine/spermine acetyltransferase (SSAT) catalyzes the acetyl-group transfer from acetyl-coenzyme A to the aminopropyl end of spermidine or spermine, producing acetylspermidine and acetylspermine. Acetylated polyamines are oxidized by polyamine oxidase (PAO) to produce hydrogen peroxide (H2O2), aminopropanal, and either putrescine or spermidine. Otherwise, spermine can be directly oxidized to spermidine by spermine oxidase (SMO) generating H2O2 and aminopropanal, which is spontaneously converted to acrolein. Other abbreviations: ornithine transcarbamylase (OTC), agmatinase (AGM), ODC antizyme (OAZ), spermidine synthase (SDS), spermine synthase (SMS), diamine oxidase (DAO). Rectangles’ color reflects the level of enzymes’ expression in relation to the healthy brain. Blue- reduction, shades of orange- increase in levels (arbitrary scale).

Figure 2. Schematic representation of the polyamine metabolism pathways in AD brain. Arginine is the mutual substrate for arginase (ARG), arginine decarboxylase (ADC), and nitric oxide synthase (NOS). Ornithine decarboxylase (ODC) decarboxylases ornithine to produce putrescine. Spermidine/spermine acetyltransferase (SSAT) catalyzes the acetyl-group transfer from acetyl-coenzyme A to the aminopropyl end of spermidine or spermine, producing acetylspermidine and acetylspermine. Acetylated polyamines are oxidized by polyamine oxidase (PAO) to produce hydrogen peroxide (H2O2), aminopropanal, and either putrescine or spermidine. Otherwise, spermine can be directly oxidized to spermidine by spermine oxidase (SMO) generating H2O2 and aminopropanal, which is spontaneously converted to acrolein. Other abbreviations: ornithine transcarbamylase (OTC), agmatinase (AGM), ODC antizyme (OAZ), spermidine synthase (SDS), spermine synthase (SMS), diamine oxidase (DAO). Rectangles’ color reflects the level of enzymes’ expression in relation to the healthy brain. Blue- reduction, shades of orange- increase in levels (arbitrary scale).