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Review
. 2022;20(8):1564-1578.
doi: 10.2174/1570159X20666220119125040.

Targeting PI3K by Natural Products: A Potential Therapeutic Strategy for Attention-deficit Hyperactivity Disorder

Tayebeh Noori  1 , Mousa Sahebgharani  2 , Antoni Sureda  3   4 , Eduardo Sobarzo-Sanchez  5   6 , Sajad Fakhri  1 , Samira Shirooie  1
Affiliations
Review

Targeting PI3K by Natural Products: A Potential Therapeutic Strategy for Attention-deficit Hyperactivity Disorder

Tayebeh Noori et al. Curr Neuropharmacol. 2022.

Abstract

Attention-Deficit Hyperactivity Disorder (ADHD) is a highly prevalent childhood psychiatric disorder. In general, a child with ADHD has significant attention problems with difficulty concentrating on a subject and is generally associated with impulsivity and excessive activity. The etiology of ADHD in most patients is unknown, although it is considered to be a multifactorial disease caused by a combination of genetics and environmental factors. Diverse factors, such as the existence of mental, nutritional, or general health problems during childhood, as well as smoking and alcohol drinking during pregnancy, are related to an increased risk of ADHD. Behavioral and psychological characteristics of ADHD include anxiety, mood disorders, behavioral disorders, language disorders, and learning disabilities. These symptoms affect individuals, families, and communities, negatively altering educational and social results, strained parent-child relationships, and increased use of health services. ADHD may be associated with deficits in inhibitory frontostriatal noradrenergic neurons on lower striatal structures that are predominantly driven by dopaminergic neurons. Phosphoinositide 3-kinases (PI3Ks) are a conserved family of lipid kinases that control a number of cellular processes, including cell proliferation, differentiation, migration, insulin metabolism, and apoptosis. Since PI3K plays an important role in controlling the noradrenergic neuron, it opens up new insights into research on ADHD and other developmental brain diseases. This review presents evidence for the potential usefulness of PI3K and its modulators as a potential treatment for ADHD.

Keywords: Attention-deficit hyperactivity disorder (ADHD); Phosphoinositide 3-kinases (PI3Ks); dopamine; etiology; natural products; neurogenesis.

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Figures

Fig. (1)
Fig. (1)
Relationships between PI3K and ADHD.
Fig. (2)
Fig. (2)
The upstream and downstream signaling pathways of PI3K, and related changes in diseases. TLR: Toll-like receptor, GPCR: G protein-coupled receptor, ETAR: Endothelin A receptor, EphB: Ephrin-B, GluT: Glucose transporter, NMDAR: N-methyl-D-aspartate receptor, Nk1R: neurokinin 1 receptor, CCR2 and CXCR3: Chemokine receptors, MOR: Morphine receptor, RTK: Receptor tyrosine kinase, NF-kB: Nuclear factor kappa-B, PI3K: Phosphoinositide 3-kinase, IRS: Insulin receptor substrate, GSK-3: Glycogen synthase kinase-3, HIF-1: Hypoxia-inducible factors, mTOR: Mammalian target of rapamycin, PIP2: Phosphatidylinositol 4,5-bisphosphate, PIP3: Phosphatidylinositol (3,4,5)-trisphosphate.
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