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Alzheimer's Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe cute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD such as the lytic replication and axonal transport of HSV-1, the various mechanisms of ZIKV neurotropism through the human protein Musashi-1 (MSI1), and the spread of SARS-CoV-2 through the transfer of the virus through the BBB endothelial cells to glial cells and then to neurons via transsynaptic transfer. We will also explore beyond these mere associations by carefully analyzing the potential mechanisms by which these viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, the dysregulation of immune responses, and the impact on protein processing (Aβ42 and hyperphosphorylated tau). Controversies and challenges of the virus–AD relationship emerge as we tease out these potential mechanisms. Looking forward, we emphasize future directions, such as distinct questions and proposed experimentations to explore, that the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development while encouraging further discussion. [ABSTRACT FROM AUTHOR]

The master molecular regulators and mechanisms determining longevity and health span include nitric oxide (NO) and superoxide anion radicals (SOR). L-arginine, the NO synthase (NOS) substrate, can restore a healthy ratio between the dangerous SOR and the protective NO radical to promote healthy aging. Antioxidant supplementation orchestrates protection against oxidative stress and damage—L-arginine and antioxidants such as vitamin C increase NO production and bioavailability. Uncoupling of NO generation with the appearance of SOR can be induced by asymmetric dimethylarginine (ADMA). L-arginine can displace ADMA from the site of NO formation if sufficient amounts of the amino acid are available. Antioxidants such as ascorbic acids can scavenge SOR and increase the bioavailability of NO. The topics of this review are the complex interactions of antioxidant agents with L-arginine, which determine NO bioactivity and protection against age-related degeneration. [ABSTRACT FROM AUTHOR]

The research not only demonstrates that only a sufficient supply of tryptophan can improve, sustain and maintain health but also indicates that increased oxidative tryptophan degradation can lead to the formation of toxic compounds that have detrimental effects. Tryptophan is a rate-limiting essential amino acid and a unique building block of peptides and proteins. Other highly relevant pathways of tryptophan are the reversible transamination to indole-3-pyruvate with the formation of the related indolic acids as well as the synthesis of indole compounds and their derivatives by side chain cleavage. Tryptophan metabolites such as melatonin and structurally related agents such as indole-3-propionic acid act as potent catalytic antioxidant and bioenergetic agents that facilitate regeneration and protection against stress and aging. [Extracted from the article]

Targeting tryptophan and the tryptophan pathway can enable novel strategies for diagnosis, prevention, treatment, and rehabilitation to improve, maintain, and restore health [[1], [3], [5], [7]]. The neuroprotective tryptophan derivative melatonin can determine the brain-heart crosstalk [[6]]. S.K.S. contributed to the writing of the manuscript and supported the corresponding author and editor, B.P., in focusing on the final tryptophan metabolites that are the topic of this Special Issue. [Extracted from the article]