From nutritional bioactive compounds to the development of therapies for neurodegenerative disorders

Common metabolic alterations are associated with the progression of a growing number of neurodegenerative disorders, characterized by different ethiopatogenesis. In the case of adrenoleukodystrophy (X-ALD), an inherited demyelinating disorder, the mutated protein (ALDP) impair lipid catabolism. During the progression of this pathology, ALDP-related proteins can be overexpressed and partially compensate the lipid metabolic impairment. Other secondary alterations develop during the progression of the disorder such as oxidative stress, inflammatory cascade, peroxisomal impairment amplify neurodegenerative conditions. The therapeutic control of these secondary events are fundamental. A crucial factor for the treatment of X-ALD and neurodegenerative conditions is the passage of drugs through the blood-brain barrier. The aim of our research was to develop a therapeutic strategy utilizing nutritional bioactive compounds. We have demonstrated that specific compounds, utilized in the dietary therapy for X-ALD, can pass through blood-brain-barrier and they are detected in the liquor of treated patients (Cappa et al., J Inherit Metab Dis, 35:899-907, 2012). We investigated the molecular mechanisms of specific bioactive compounds to develop a dietary strategy aimed to modulate the progression of neurodegenerative disorders.