Neurodegeneration in Cognitive Impairment and Mood Disorders for Experimental, Clinical and Translational Neuropsychiatry

Battaglia, Simone; Avenanti, Alessio; Vécsei, László; Tanaka, Masaru

doi:10.3390/biomedicines12030574

Cited by 14 publications

(13 citation statements)

References 110 publications

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“…1 H (500 MHz, DMSO), δ(ppm): 2.00 (3H, s); 2.85 (6H, d, J = 4.8 Hz); 3.31 (2H, q, J = 6.1 Hz); 3.66 (2H, q, J = 5.9 Hz), 7.32 (1H, t, J = 7.6 Hz); 7.66 (1H, t, J = 7.2 Hz); 7. 77 S5 and S6).…”

Section: Behavioral Testsmentioning

confidence: 90%

“…KYNA has been implicated in various neuropsychiatric and neurodegenerative disorders, and KYNA levels in the brain and body are influenced by factors such as inflammation, stress, aging, and genetic variation [ 62 , 65 , 66 , 67 , 68 , 69 ]. Furthermore, recent research has shed light on the mechanism of emotional learning, including its potential role in modulating affective motor function and emotional responses [ 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. The neural substrates involved in emotional learning, particularly KYNA, suggest a plausible impact on the limbic system, including structures such as the amygdala and prefrontal cortex, which are known to be involved in emotional regulation and associative learning [ 74 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ].…”

Section: Introductionmentioning

confidence: 99%

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The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain

Martos,

Lőrinczi,

Szatmári

et al. 2024

IJMS

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The central nervous system (CNS) is the final frontier in drug delivery because of the blood–brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions, and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain-modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically, SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open-field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 μmol/4 μL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 μmol/4 μL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

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Section: Behavioral Testsmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain

Martos,

Lőrinczi,

Szatmári

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Hence, alternative treatments may improve patients' quality of life with AD. Novel therapeutic opportunities for AD strategies include improving cognitive function and reducing amyloid deposition, opening up new treatment options, and including monoclonal antibodies [6,[19][20][21][22][23][24][25]. Traditionally, AD has been treated with drugs that relieve symptoms, such a cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and N-methyl-D aspartate receptor (NMDAR) antagonists (memantine).…”

Section: Introductionmentioning

confidence: 99%

Ginkgo biloba: A Leaf of Hope in the Fight against Alzheimer’s Dementia: Clinical Trial Systematic Review

Pagotto,

Santos,

Osman

et al. 2024

Antioxidants

Self Cite

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Alzheimer’s disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords—GB in AD and dementia—yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show that Ginkgo biloba has promising potential for the treatment of these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

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“…We investigate the various impacts of time on neural circuits and cognitive responses. Our research spans studying how the brain can adjust and recuperate following a stroke, a process known as neuroplasticity, to exploring the intricate link between age and behavior [1][2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

A Decade of Dedication: Pioneering Perspectives on Neurological Diseases and Mental Illnesses

Tanaka,

Vécsei

2024

Biomedicines

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Neurodegeneration in Cognitive Impairment and Mood Disorders for Experimental, Clinical and Translational Neuropsychiatry

Abstract: Neurodegeneration poses a significant challenge for the fields of neuroscience and medicine, as it is the underlying cause of the development and advancement of numerous neurodegenerative and psychiatric disorders [...]

Cited by 14 publications

References 110 publications

The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain

The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain

Ginkgo biloba: A Leaf of Hope in the Fight against Alzheimer’s Dementia: Clinical Trial Systematic Review

A Decade of Dedication: Pioneering Perspectives on Neurological Diseases and Mental Illnesses

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