α-黑素细胞刺激作为阿尔茨海默病的潜在治疗药物

Title:α-Melanocyte Stimulating Hormone as a Potential Therapy for Alzheimer's Disease

Volume: 14 Issue: 1

Author(s): Keran Ma and JoAnne McLaurin

Affiliation:

关键词: 阿尔茨海默病，α-促黑素细胞激素，神经保护，生长抑素

摘要: Background: Alzheimer's disease (AD) is characterized by accumulation and aggregation of beta-amyloid peptide, neurofibrillary tangles of hyperphosphorylated tau, neuroinflammation, synaptic degeneration and eventual neuronal cell loss. Current treatment options for AD provide temporary symptomatic relief in a subset of patients. These drugs include cholinesterase inhibitors that improve cholinergic innervation such as rivastigmine, donepezil and galatamine. In addition, memantine, a Nmethyl- D-aspartate antagonist, is used to treat moderate to severe AD by reducing excitotoxicity. It has been proposed that increased excitation and decreased inhibition lead to aberrant excitatory neuronal activity and cognitive deficits in AD.

Methods: We undertook a search of the literature using bibliographic databases to identify publications that were related to neuronal activity in Alzheimer's disease. We further delineated the publications to determine inclusion/exclusion criteria based on relevance to increased excitation or decreased inhibition of neuronal networks in both human patients and rodent models. The final criteria related to the potential use of α-Melanocyte stimulating hormone (α-MSH) as a potential treatment strategy for Alzheimer's disease. These data were utilized to obtain the content of this review.

Results: We identified 156 peer-reviewed publications that met our criteria and describe the findings here. Rodent models of AD and ageing both exhibit cognitive deficits and loss of inhibitory GABAerigc interneurons. α-Melanocyte stimulating hormone is a neuropeptide that is down-regulated in the brain and cerebrospinal fluid of AD patients. α-MSH has many functions in the central nervous system including neuroprotective and anti-inflammatory effects that target multiple aspects of the AD pathology. α-MSH treatment promoted the survival of GABAergic interneurons in the hippocampus and improved spatial memory as well as alterations in anxiety in a mouse model of AD. The somatostatin expressing subpopulation of GABAergic interneurons are particularly preserved by α-MSH treatment. Somatostatin has been implicated in hippocampal-dependent cognitive tasks. Somatostatin-expressing interneurons have also been shown to play an important role in maintaining excitatory-inhibitory balance. α-MSH preserved GABAergic interneurons and by preventing the loss of the somatostatin subpopulation, it improved cognitive function.

Conclusion: α-MSH is a novel candidate for the treatment of AD but its therapeutic potential in AD patients remains to be investigated.

Cite this article as:

Keran Ma and JoAnne McLaurin , α-Melanocyte Stimulating Hormone as a Potential Therapy for Alzheimer's Disease, Current Alzheimer Research 2017; 14 (1) . https://dx.doi.org/10.2174/1567205013666160819130641

DOI https://dx.doi.org/10.2174/1567205013666160819130641	Print ISSN 1567-2050
Publisher Name Bentham Science Publisher	Online ISSN 1875-5828