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α-Lipoic Acid, an Organosulfur Biomolecule a Novel Therapeutic Agent for Neurodegenerative Disorders: An Mechanistic Perspective

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Abstract

Lipoic acid (α-LA) (1,2-dithiolane3-pentanoic acid (C8H14O2S2) is also called thioctic acid with an oxidized (disulfide, LA) and a reduced (di-thiol: dihydro-lipoic acid, DHLA) form of LA. α-LA is a potent anti-oxidative agent that has a significant potential to treat neurodegenerative disorders. α-LA is both hydrophilic and hydrophobic in nature. It is widely distributed in plants and animals in cellular membranes and in the cytosol, which is responsible for LA’s action in both the cytosol and plasma membrane. A systematic literature review of Bentham, Scopus, PubMed, Medline, and EMBASE (Elsevier) databases was carried out to understand the Nature and mechanistic interventions of the α-Lipoic acid for central nervous system diseases. Moreover, α-LA readily crosses the blood-brain barrier, which is a significant factor for CNS activities. The mechanisms of α-LA reduction are highly tissue-specific. α-LA produces its neuroprotective effect by inhibiting reactive oxygen species formation and neuronal damage, modulating protein levels, and promoting neurotransmitters and anti-oxidant levels. Hence, the execution of α-LA as a therapeutic ingredient in the therapy of neurodegenerative disorders is promising. Finally, based on evidence, it can be concluded that α-LA can prevent diseases related to the nervous system.

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Abbreviations

α-LA:

Alpha lipoic acid

PD:

Parkinson’s disease

AD:

Alzheimer’s disease

SCI:

spinal cord injury

MDA:

Malondialdehyde

TBARS:

Thiobarbituric acid reactive substances

ROS:

Reactive oxygen species

NOS:

Nitric oxide synthase

MCAO:

Middle cerebral artery occlusion

SOD:

Superoxide Dismutase

ATP:

Adenosine triphosphate.

CIRI:

Cerebral ischemia and reperfusion injury

PGC1α:

Peroxisome proliferator-activated receptor-gamma coactivator

MS:

Multiple sclerosis

BBB:

Blood-brain barrier

DHLA:

Dihydrolipoic acid

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Acknowledgements

The authors are grateful to the Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, Punjab, India for providing the necessary facilities to carry out the research work.

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    Authors and Affiliations

    1. Chitkara College of Pharmacy, Chitkara University, 140401, Punjab, India

      Heena Khan & Thakur Gurjeet Singh

    2. Department of Pharmacology, Central University, 151001, Bathinda, India

      Randhir Singh Dahiya

    3. Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, 21442, Jeddah, Saudi Arabia

      Mohamed M. Abdel-Daim

    4. Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, 41522, Ismailia, Egypt

      Mohamed M. Abdel-Daim

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    1. Heena Khan
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    Credit Author Statement:Conceptualization: Conceived and designed the experiments: Thakur Gurjeet Singh, Heena Khan, Randhir Singh. Analyzed the data: Heena Khan, Thakur Gurjeet Singh Wrote the manuscript: Heena Khan Editing of the Manuscript: Thakur Gurjeet Singh Critically reviewed the article: Randhir Singh, Thakur Gurjeet Singh Supervision: Thakur Gurjeet Singh, Mohamed M. Abdel-Daim.

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    Khan, H., Singh, T.G., Dahiya, R.S. et al. α-Lipoic Acid, an Organosulfur Biomolecule a Novel Therapeutic Agent for Neurodegenerative Disorders: An Mechanistic Perspective. Neurochem Res 47, 1853–1864 (2022). https://doi.org/10.1007/s11064-022-03598-w

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