15-deoxy-Δ12,14-prostaglandin J2 in neurodegenerative diseases and cancers

Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) appear to have no connection with cancers. In the view of cell death, however, common ground can be found between neuronal and non-neuronal diseases [1]. AD and PD are ascribed to the cell death of neurons, which should be alive under healthy conditions. In contrast, cancers are attributed to the proliferation of abnormal cells, which should be dead appropriately. The uncontrollability of cell death contributes to the pathogenesis of these diseases. Are there endogenous ligands related to these diseases? An endogenous anticancer 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) has been the common factor associated with cancers and neurodegenerative diseases (Figure 1). In cancer cells, 15d-PGJ2 has been reported to induce apoptosis, which was dependent on or independent of its nuclear receptor, peroxysome-proliferator activated receptor γ (PPARγ) [1, 2]. PD is characterized by the loss of dopaminergic neurons projecting from substantia nigra pars compacta to striatum, and disables motor functions [1]. Subchronic microinfusion of a precursor of 15d-PGJ2, PGJ2, into the substantia nigra/striatum has been reported to induce PDlike features [3]. Unilateral lesions of the dopaminergic nigrostriatal system caused circling behavior, which was ascribed to the functional imbalance between the dopaminergic nigrostriatal pathways on the two sides of the brain. We confirmed that the unilateral injection of 15d-PGJ2 into striatum induced circling in the ipsilateral direction (data not shown). Thus, 15d-PGJ2 could act as a neurodegenerative mediator of PD. Among various PGs, a precursor of 15d-PGJ2, PGD2, is most abundant in the central nervous system, and increased in cerebral cortex of AD patients [4]. AD is characterized pathologically by neurofibrillary tangles and senile plaques, which are followed by neuronal loss