Abstract
Chronic neurodegenerative diseases are a group of devastating neurological disorders that result in significant morbidity and mortality in the elderly population worldwide. Recent researches have shown some interesting associations of the classical antiobesity hormone leptin with two most important neurodegenerative diseases—Alzheimer’s disease (AD) and Parkinson’s disease (PD). Although several clinical studies have found the procognitive and memory-enhancing role of this peptide hormone in leptin-deficient patients, surprisingly it has not been used in any clinical trials involving patients with developing or full-blown neurodegenerative conditions. This review article is an attempt to bring together the existing information about the clinical associations of leptin with AD and PD. It starts with the basic understanding of leptin action in the brain and its derangements in these diseases and eventually discusses the potential of this hormone as a neuroprotective agent in clinical scenario.
Highlights
Aging-related chronic neurodegenerative diseases constitute a spectrum of neurological disorders characterized by a gradual loss of neuronal functions resulting from the toxicity of accumulated misfolded proteins [1,2,3,4,5]
A lot of theories and therapeutic targets have been identified underlying these debilitating diseases and various risk factors have been implicated in their pathogenesis, this spectrum of challenging disorders remains an enigma to the physicians and the scientists
This has been accounted for a number of reasons like reduction in the STAT3 activation downstream of the leptin receptor (Ob-R) signaling pathway, decrease in the Ob-R expression due to reduced uptake of leptin by the hypothalamic nuclei, impaired suppression of hypothalamic neuropeptide Y (NPY) mRNA levels, and increased inhibition of Ob-R signal transduction owing to the age-dependent increase in the level of suppressor of cytokine signaling-3 (SOCS-3) and protein tyrosine phosphatase 1B [25,26,27,28,29]
Summary
Aging-related chronic neurodegenerative diseases constitute a spectrum of neurological disorders characterized by a gradual loss of neuronal functions resulting from the toxicity of accumulated misfolded proteins [1,2,3,4,5]. Recent studies have found an interesting role of this hormone in various neurological functions like regulation of hypothalamic neuronal excitability, inhibition of hippocampal neurons, regulation of activity of the mesolimbic dopaminergic system, and modulation of synaptic plasticity and novel antidepressant actions [17,18,19,20]. Many of these neurological properties of leptin are currently being probed in order to get a strong foothold of the therapeutic implications for neurological disorders. The present paper discusses the various aspects of leptin as a potential therapeutic molecule in the treatment of neurodegeneration along with the findings of some recent clinical studies showing its association with this group of disorders followed by a review of the clinical trials using leptin and its prospect as therapeutic agent in neurodegenerative diseases
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