The Thiol Antioxidant Lipoic Acid and Alzheimer’s Disease

Ooi, Lezanne; Patel, Mayuri; Müench, Gerald

doi:10.1007/978-3-642-30018-9_84

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…It is engaged around amyloid plaques, surrounded by activated astrocytes and microglia, and is characterized by elevated levels of free radicals and pro-inflammatory cytokines [61], with TNF-α being considered an indicator from mild cognitive impairment to AD [59,62]. ALA has multiple and complex effects in this way, namely scavenging ROS, transition metal ions, increasing the levels of reduced glutathione [59,63], scavenging of lipid peroxidation products [62,64,65] and even acting on signal transduction pathways [63,66]. Similarly, Dinicola et al [67] found that ALA downregulated the levels of the inflammatory cytokines IL-1B and IL-6 in SK-N-BE human neuroblastoma cells through DNA methylation-dependent modulation, paving the way for the impact of epigenetic mechanisms in AD control/prevention.…”

Section: α-Lipoic Acid Pharmacological Activities: An Overviewmentioning

confidence: 99%

Insights on the Use of α-Lipoic Acid for Therapeutic Purposes

et al. 2019

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α-lipoic acid (ALA, thioctic acid) is an organosulfur component produced from plants, animals, and humans. It has various properties, among them great antioxidant potential and is widely used as a racemic drug for diabetic polyneuropathy-associated pain and paresthesia. Naturally, ALA is located in mitochondria, where it is used as a cofactor for pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase complexes. Despite its various potentials, ALA therapeutic efficacy is relatively low due to its pharmacokinetic profile. Data suggests that ALA has a short half-life and bioavailability (about 30%) triggered by its hepatic degradation, reduced solubility as well as instability in the stomach. However, the use of various innovative formulations has greatly improved ALA bioavailability. The R enantiomer of ALA shows better pharmacokinetic parameters, including increased bioavailability as compared to its S enantiomer. Indeed, the use of amphiphilic matrices has capability to improve ALA bioavailability and intestinal absorption. Also, ALA’s liquid formulations are associated with greater plasma concentration and bioavailability as compared to its solidified dosage form. Thus, improved formulations can increase both ALA absorption and bioavailability, leading to a raise in therapeutic efficacy. Interestingly, ALA bioavailability will be dependent on age, while no difference has been found for gender. The present review aims to provide an updated on studies from preclinical to clinical trials assessing ALA’s usages in diabetic patients with neuropathy, obesity, central nervous system-related diseases and abnormalities in pregnancy.

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Section: α-Lipoic Acid Pharmacological Activities: An Overviewmentioning

confidence: 99%

Insights on the Use of α-Lipoic Acid for Therapeutic Purposes

et al. 2019

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“…Dihydrolipoic acid is a hydrolyzed form of α-LA. Several studies indicated DHLA as a metal chelator, antioxidant, radical scavenger and anti-in ammatory agent [20][21][22]. Both α-LA and DHLA have also been proposed to have neuroprotective effects and can be an option in treating AD [23][24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant dihydrolipolic acid protects against aluminum-induced toxicity in Alzheimer's model

Sanajou

Yirün

Demirel

et al. 2023

Preprint

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Dihydrolipoic acid (DHLA) is a natural antioxidant that is recognized as being useful in combating metal toxicity and oxidative stress. It can protect cells from environmental contaminants and may be beneficial in treating neurodegenerative diseases by protecting against oxidative damage and chronic inflammation. Therefore, this study aimed to investigate the possible neuroprotective effects of DHLA against aluminum-induced toxicity in an in vitro Alzheimer’s disease (AD) model. The study focused on the glycogen synthase kinase3 (GSK3) pathway, and the Wnt signaling. A differentiated SH-SY5Y cell line model of AD was developed, and the study groups were as follows: control, Al, DHLA, Al-DHLA, AD, AD-Al, AD-DHLA, and AD-Al-DHLA. The impact of DHLA on oxidative stress parameters was evaluated, and GSK3 pathway was evaluated by measuring GSK3-β, human serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA), protein phosphatase 2A (PP2A) levels, and human RAC-alpha serine/threonine-protein kinase (AKT1). The Wnt signaling pathway was evaluated by measuring canonical Wingless and Int-1/β-catenin (Wnt/β-catenin) on different study groups. Exposure to DHLA reduced oxidative stress by dramatically lowering reactive oxygen species levels, protecting against protein oxidation, and limiting malonaldehyde production. Additionally, the total antioxidant capacity of DHLA-treated groups increased drastically. Furthermore, upregulation of Wnt signaling and downregulation of GSK3 pathways were observed in the groups treated by DHLA. Overall, the neuroprotective effects of DHLA, especially by reducing oxidative stress and regulating key imbalanced pathways in AD disease, make it a good candidate to be added to AD patients' treatment regimens.

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“…Our study employed differentiated SH-SY5Y cells, which exhibit Several studies indicated DHLA as a metal chelator, antioxidant, radical scavenger, and anti-inflammatory agent (Al-Otaibi et al, 2018;Maczurek et al, 2008;Ooi et al, 2012). Both α-LA and DHLA have also been proposed to have neuroprotective effects and can be an option for treating AD (Greenamyre et al, 1994;Holmquist et al, 2007;Khan et al, 2022;Koenig & Meyerhoff, 2003).…”

Section: Discussionmentioning

confidence: 99%

Antioxidant dihydrolipolic acid protects against in vitro aluminum‐induced toxicity

Sanajou

Yirün

Demirel

et al. 2023

J of Applied Toxicology

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Dihydrolipoic acid (DHLA) is a natural antioxidant known for its ability to counteract metal toxicity and oxidative stress. It has shown the potential to safeguard cells from harmful environmental substances. It may hold therapeutic benefits in treating neurodegenerative disorders by defending against oxidative damage and chronic inflammation. Thus, this study aimed to explore the potential neuroprotective effects of DHLA against aluminum (Al)‐induced toxicity using an Alzheimer's disease (AD) model in vitro. The study focused on two important pathways: GSK‐3β and the Wnt signaling pathways. The SH‐SY5Y cell line was differentiated to establish AD, and the study group were as follows: control, Al, DHLA, Al‐DHLA, AD, AD‐Al, AD‐DHLA, and AD‐Al‐DHLA. The impact of DHLA on parameters related to oxidative stress was assessed. The activity of the GSK‐3β pathway was measured by evaluating the levels of PPP1CA, PP2A, GSK‐3β, and Akt. The Wnt signaling pathway was assessed by measuring Wnt/β‐catenin in the different study groups. Exposure to DHLA significantly reduced oxidative stress by effectively decreasing the levels of reactive oxygen species, thereby protecting against protein oxidation and limiting the production of malonaldehyde. Moreover, the DHLA‐treated groups exhibited a remarkable increase in the total antioxidant capacity. Furthermore, the study observed an upregulation of the Wnt signaling pathway and a downregulation of the GSK‐3β pathway in the groups treated with DHLA. In summary, the neuroprotective effects of DHLA, primarily achieved by reducing oxidative stress and modulating critical imbalanced pathways associated with AD, indicate its potential as a promising addition to the treatment regimens of AD patients.

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The Thiol Antioxidant Lipoic Acid and Alzheimer’s Disease

Cited by 5 publications

References 42 publications

Insights on the Use of α-Lipoic Acid for Therapeutic Purposes

Insights on the Use of α-Lipoic Acid for Therapeutic Purposes

Antioxidant dihydrolipolic acid protects against aluminum-induced toxicity in Alzheimer's model

Antioxidant dihydrolipolic acid protects against in vitro aluminum‐induced toxicity

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