“D-Neuron Protection / Activation (DPA) Therapy”: New Strategy for Treatment of Neuropsychiatric Illnesses

Abstract

Keiko Ikemoto

Recent progress of pharmacotherapy enabled anti-amyloid and anti-tau immunotherapy for Alzheimer disease. Yet, non-pharmacological factors, alimentation, sleep, exercise, stress-management or cognition stimulation, has also been emphasized. The D-neuron, that is β�?�phenylethylamine (PEA) neuron, or TAAR1 ligand neuron, localizes from D1 (spinal cord) to D18 (cerebral cortex) in caudo-rostral order of mammalian brains. In post-mortem brains with schizophrenia, D-neurons lacked in the nucleus accumbens (Acc, D16), a projection field of mesolimbic dopamine system. This lead to establish “D-cell hypothesis of mental illnesses”, and a novel therapy aimed at protection and activation of D-neuron, “D-neuron protection / activation (DPA) therapy”. As histochemical visualization of D-neurons is a no easy technique, D-neuron activity in the CNS should initially be evaluated indirectly by biomarkers, such as PEA, brain-derived neurotrophic factor (BDNF), tyramine, octopamine and β�?�endorphin, and biomarkers of inflammation, such as CRP, TNF and IL-6 in cerebrospinal fluid (CSF), serum or urine. Reliable biomarkers of mental / cognitive functions should also be employed. “DPA therapy” is a novel cellular level treatment of neuropsychiatric illnesses including dementia.

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