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CN-122005619-A - Clostridium bacteria with preventing or treating effect on neurodegenerative brain diseases and application thereof

CN122005619ACN 122005619 ACN122005619 ACN 122005619ACN-122005619-A

Abstract

The invention discloses a Clostridium strain with a preventive or therapeutic effect on neurodegenerative brain diseases and application thereof. The Clostridium strain of the present invention has a neuroprotective effect and a remarkable improving effect in animal models of degenerative brain diseases such as parkinson's disease, alzheimer's disease, etc., and has an effect of relieving dyskinesia and non-dyskinesia including cognitive dysfunction and gastrointestinal dysfunction, etc., in animal models of parkinson's disease, so that the strain can be effectively applied to foods and medicines for preventing or treating neurodegenerative brain diseases including parkinson's disease, alzheimer's disease, cognitive dysfunction, etc.

Inventors

  • DENG XUEYANG
  • WANG RUI
  • LI JIAYUAN
  • WANG XINRAN

Assignees

  • 中国药科大学

Dates

Publication Date
20260512
Application Date
20260120

Claims (9)

  1. Use of a clostridium strain for the preparation of a medicament for the prevention and/or treatment of neurodegenerative brain diseases.
  2. 2. The use according to claim 1, wherein the Clostridium strain comprises a selenophosphate synthase.
  3. 3. The use according to claim 2, characterized in that the Clostridium strain further comprises selenocysteine lyase and/or thioredoxin reductase.
  4. 4. The use according to any one of claims 1 to 3, wherein the Clostridium strain comprises at least one of strain Clostridium Butyricum, strain Clostridium Saccharobutylicum and strain Clostridium Diolis.
  5. 5. The use according to any one of claims 1-3, wherein the degenerative brain disease is parkinson's disease, alzheimer's disease, mild cognitive impairment, meningitis, stroke, dementia, huntington's disease, or creutzfeld-jakob disease.
  6. 6. The use according to claim 5, wherein said parkinson's disease comprises selenium deficient parkinson's disease.
  7. 7. The use according to claim 5, wherein the Clostridium strain reduces parkinson's disease including dyskinesia and non-dyskinesia.
  8. 8. The use according to claim 7, wherein the non-movement disorders comprise cognitive disorders, olfactory disorders or gastrointestinal disorders, etc.
  9. 9. Use according to any one of claims 1-3, characterized in that a Clostridium strain is used in a pharmaceutical composition for the treatment of neurodegenerative brain diseases, said composition comprising, as active ingredient, a genus strain, a culture comprising said genus strain, or a dried product of a culture comprising said genus strain.

Description

Clostridium bacteria with preventing or treating effect on neurodegenerative brain diseases and application thereof Technical Field The present invention relates to a Clostridium strain having a prophylactic or therapeutic effect on neurodegenerative brain diseases and an application thereof. Background Neurodegenerative diseases (Neurodegenerative diseases, ND) are a type of chronic diseases characterized by progressive degeneration of neurons and progressive loss of nerve function, mainly involving the central nervous system such as the brain, spinal cord, etc. ND is classified into two major categories based on clinical characteristics, diseases based on movement dysfunction, such as Parkinson's Disease (PD), huntington's Disease (HD), and the like, and diseases based on memory cognitive impairment, such as Alzheimer's Disease (AD) and other types of dementia. The disease is well developed in middle-aged and elderly people, and the incidence rate of the disease is obviously increased along with the acceleration of the global aging process. Parkinson's Disease (PD) is a neurodegenerative Disease, and the incidence and prevalence of PD gradually increase with age, and the incidence of PD is becoming younger and younger with the acceleration of industrialization progress and changes in environmental factors. Clinically, the main symptoms of PD patients include dyskinesias such as bradykinesia, resting tremor, myotonia and gait changes, and almost all patients show non-dyskinesias such as hyposmia, constipation, sleep disorder and hypomnesia. Alpha-syn, a protein with a molecular weight of 14.5kDa, is mainly present at the synaptic terminals of the nervous system and is responsible for mediating synaptic function and neuroplasticity. When the 53 rd amino acid coded by the gene is mutated from alanine to threonine (A53T mutation), the misfolding of alpha-syn is promoted and the alpha-syn is aggregated to form amyloid fibrils, and the abnormal aggregate has the characteristic of Raney virus and can induce the alpha-syn with normal physiological activity to be misfolded and further aggregated, so that the solubility of the alpha-syn is continuously reduced, and the alpha-syn fibrils are continuously increased and form a lewy body. Abnormal aggregation of α -syn not only results in dysfunction of neurotransmitter release, but also causes dysfunction of calcium homeostasis, mitochondrial dysfunction, impaired protein homeostasis, and neuroinflammation, ultimately promoting the development of PD. Selenium is a trace element essential to the human body, and both deficiency and excess causes related diseases, and also shows strong association with PD. Selenium exists in nature in inorganic forms (selenates, selenites) and organic forms (selenomethionines, selenocysteines) and is mainly absorbed by the human body in the form of food. The total content of selenium taken by human body is lower in brain compared with peripheral tissue organs such as blood, but the selenium in brain is least easy to consume. When the human body is under the condition of low level of selenium, selenium in the brain is still preserved, which indicates that selenium is an indispensable trace element for the brain. Clinical studies indicate that the level of selenium in the blood of PD patients is low, and an increase in blood selenium level is inversely related to the incidence of PD, and PD patients with lower blood selenium levels often perform worse in a neural coordination test. Clostridium strains, including Clostridium Butyricum strain, are a butyrate-producing human intestinal symbiont and have been safely used as probiotics for decades. The Clostridium Butyricum strain has been investigated for potential protective or ameliorating effects on a variety of human diseases including acquired intestinal infections, intestinal lesions, irritable bowel syndrome, inflammatory bowel disease, metabolic diseases and colorectal cancer. Contains Clostridium Saccharobutylicum strain, which can efficiently produce n-butanol and other valuable chemicals from plant materials through acetone-butanol-ethanol (ABE) fermentation. The inclusion of Clostridium Diolis strain was previously considered one of the best natural producers of 1, 3-propanediol because of its apparent substrate tolerance, yield and productivity. The Clostridium strain comprises a selenophosphate synthase. Selenophosphate synthase is an enzyme that synthesizes selenophosphate using selenium and ATP, and is essential for the biological utilization of selenium, especially for the synthesis of the atypical amino acid selenocysteine (Sec). Thus, selenophosphate synthases are fundamental to all functions of selenoproteins, including redox homeostasis, protein quality control, hormonal regulation, metabolism, etc. Selenoproteins are a group of enzymes containing selenocysteine (Sec), an atypical seleno-containing amino acid, usually located at the active site, encoded by UGA, which is us