Abstract
The incidence of neurodegenerative diseases has increased greatly worldwide due to the rise in life expectancy. In spite of notable development in the understanding of these disorders, there has been limited success in the development of neuroprotective agents that can slow the progression of the disease and prevent neuronal death. Some natural products and molecules are very promising neuroprotective agents because of their structural diversity and wide variety of biological activities. In addition to their neuroprotective effect, they are known for their antioxidant, anti-inflammatory and antiapoptotic effects and often serve as a starting point for drug discovery. In this review, the following natural molecules are discussed: firstly, kynurenic acid, the main neuroprotective agent formed via the kynurenine pathway of tryptophan metabolism, as it is known mainly for its role in glutamate excitotoxicity, secondly, the dietary supplement pantethine, that is many sided, well tolerated and safe, and the third molecule, α-lipoic acid is a universal antioxidant. As a conclusion, because of their beneficial properties, these molecules are potential candidates for neuroprotective therapies suitable in managing neurodegenerative diseases.
Highlights
Neuronal damage in the central nervous system (CNS) is universal in neurodegenerative diseases (NDs) [1]
The kynurenine pathway (KP) is comprised of several enzymatic steps (Figure 3), which lead to the formation of NAD+, which has a pivotal role in different cellular functions (energy dioxygenase (IDO) [35] and tryptophan 2,3-dioxygenase (TDO) enzymes [36], the ratelimiting enzymes of the pathway [37]
The KP is comprised of several enzymatic steps (Figure 3), which lead to the formation of NAD+, which has a pivotal role in different cellular functions [28]
Summary
Neuronal damage in the central nervous system (CNS) is universal in neurodegenerative diseases (NDs) [1]. The KP is comprised of several enzymatic steps (Figure 3), which lead to the formation of NAD+ , which has a pivotal role in different cellular functions (energy dioxygenase (IDO) [35] and tryptophan 2,3-dioxygenase (TDO) enzymes [36], the ratelimiting enzymes of the pathway [37]. L-tryptophan converting IDO and TDO depict the rate-limiting enzymes of the pathway be further degraded through three distinct routes to form several neuroactive metabolites: kynurenic acid, 3-hydroxy-L[37]. N-methyl-aspartic acidproduction receptor; 3HAO: oxidase; ACMSD: and Dfree radical [40], 3-hydroxyanthranilate while neuroprotection can be exerted2-amino-3by kynurenic carboxymuconate-semialdehyde decarboxylase; AMSDH: 2-aminomuconate-6-semialdehyde dehydrogenase; IDO/TDO: TRP: acid (color green) by acting as an antagonist at the NMDA receptor [41]. Three potential therapeutic strategies for drug development are known: (i) KYNA analogs with better bioavailability and higher affinity to the binding sites of excitatory receptors; (ii) prodrugs of KYNA, which cross the BBB combined with an organic acid transport inhibitor to increase brain KYNA levels; and (iii) inhibitors of enzymes of the KP [54]
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