CN116990520A - Protein rod-shaped body marker and application thereof - Google Patents
Protein rod-shaped body marker and application thereof Download PDFInfo
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Abstract
The invention provides a protein rod-shaped body marker and application thereof. The protein rod markers have a hollow rod-like structure and are present within excitatory neuronal cells. The protein rod structure is related to maintaining normal physiological functions of neurons, can influence somatosensory nerve information transmission function, and can provide markers or detection standards for diagnosis and treatment of diseases related to somatosensory nerve disorder.
Description
Technical Field
The invention belongs to the technical field of biology, and particularly relates to a protein rod-shaped body marker and application thereof.
Background
Somatosensory, as the name implies, refers to the perception of the body, involving sensory experiences derived from the body surface, such as pain, touch or temperature, and sensory experiences derived from deeper tissues (e.g., viscera, muscles or joints). In human and rodent studies, lack of a smooth touch can lead to impaired somatosensory development, increased palpation, and defects in social behavior and cognitive ability. Notably, over 94% of Autism Spectrum Disorder (ASD) children report the appearance of high or low sensitivity in a number of sensory areas. Indicating that the handling of emotional haptics by people with more autism-related features is impaired. The thalamus has long been known as a relay station that transmits information to the cortex. The processing of somatosensory information is accomplished in the interaction between the different somatosensory cortex and thalamus. The establishment of topographical connections between multiple thalamocortical areas and somatosensory cortex is the basis of sensory function, but the molecular signaling that controls thalamocortical axonal guidance and synaptic targeting is not fully understood.
It is not uncommon for the structure of intracellular protein rods to be similar to endosomes on neuronal cell bodies. In 1969, researchers have found that eosinophils composed of proteins exist in certain neurons in the thalamus of aging mice, which can be labeled with eosin acidic dyes. Such acidophiles are typically enclosed in a clear space, which is usually circular, but sometimes oval or rod-shaped, occasionally with a pale disk or dish in between. But they could not be detected in the thalamus of low-age mice.
By 1994, a rod-like structure called Hirano bodies consisting of actin skeleton and its binding proteins was found in neuronal cells of patients suffering from amyotrophic lateral sclerosis and Parkinson-dementia syndrome (ALS-PDC), with a diameter of 10-12nm, a gap of 12nm, and its distribution limited to the Ammon' short and nearby regions of the hippocampus.
In recent years, studies have shown that under neuronal stress conditions, cofilin and saturated F-actin fragments can undergo oxidative crosslinking and bind together to form Cofilin-actin sticks, forming rod-like cells in large numbers within neurons surrounding cerebral ischemic lesions. Several tens of different rods have been reported to be identified so far, such as neurofibrillary tangles of alzheimer's disease, pi Keti (Pick bodies), lewy bodies (Lewy bodies) and Lafora bodies, etc., which occur almost all in senile and degenerative diseases, are used for diagnosis of nervous system diseases, providing clues for the nature of degenerative diseases.
The Coronin family of proteins, in turn, are very conserved actin-scaffold binding proteins that are involved in regulating various fate-determining events of cells, such as cell movement, immune response, tumorigenesis, and signal transduction, etc., by binding to actin. Coronin2B is specifically highly expressed in the nervous system. However, little is known about the neurological function of Coronin 2B.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a protein rod-shaped body marker, a positioning method and application thereof. The invention aims to provide a novel protein rod-shaped body structure and application thereof in somatosensory nerve disorder. The protein rod structure is related to maintaining normal physiological functions of neurons, can influence somatosensory nerve information transmission function, and can provide markers or detection standards for diagnosis and treatment of diseases related to somatosensory nerve disorder.
In order to achieve the aim of the invention, the invention adopts the following technical scheme:
in a first aspect, the present invention provides a protein rod marker having a hollow rod-like structure, and the protein rod marker is present within the body of an excitatory neuron cell.
In the invention, coronin2B is found to form a novel rod-shaped structure (Coronin 2B rod, namely the protein rod-shaped body marker disclosed by the invention) in a nuclear area related to thalamus and somatosensory functions of mice of a certain age for the first time. The protein rod-shaped body marker is a disease marker related to somatosensory nerve disorder, the disease marker related to somatosensory nerve disorder is a protein rod-shaped body with a hollow rod-shaped structure, and the protein rod-shaped body marker exists in excitatory neuron cell bodies.
The thalamus posterior nucleus (PO) is then typically a higher order nucleus whose axonal tip climbs directly to and receives subcortical input from the fifth layer of the somatosensory cortex. The invention provides a protein rod marker Coronin2B, which is a special rod structure (Coronin 2B rod) existing in neuron cells of thalamus nucleus sensing area of adult mice, and the structure shuttles between glutamatergic neurons of PO area in large quantity, and is associated with intracellular and extracellular substances and rapid transport of the substances.
In addition, the Coronin2B rod neurons and the somatic cortex of beard have a direct projection relationship, and further the invention discovers that the transgenic mice knocked out Coronin2B show obvious somatic disorder induced by beard, and physiological experiments also show that the calcium activity of PO zone neurons is inhibited, and a series of abnormal functions of the somatic cortex with lower degree of neuron electrical activation are also discovered. This is a great aid in fully understanding the communication between thalamus somatosensory areas.
The Coronin protein family is a very conserved actin-scaffold binding protein that is involved in regulating various fate-determining events of cells, such as cell movement, immune response, tumorigenesis, and signal transduction, etc., by binding to actin. The central nervous system is where Coronin2B is highly expressed specifically, from the onset of neural development to the extinction of the brain, as compared to other members. However, coronin2B has little research into the functioning of the nervous system.
In the present invention, the protein rod-like body marker may have a length of 5 to 10. Mu.m, for example, 5. Mu.m, 6. Mu.m, 7. Mu.m, 8. Mu.m, 9. Mu.m, 10. Mu.m, etc.
In the present invention, the cross section of the protein rod-like body marker is irregularly rounded. The protein rod-like body marker may have an inner diameter of 1 to 3. Mu.m, for example, 1 μm, 1.2 μm, 1.5 μm, 1.6 μm, 1.7 μm, 1.8 μm, 1.9 μm, 2.0 μm, 2.1 μm, 2.2 μm, 2.3 μm, 2.4 μm, 2.5 μm, 2.8 μm, 3 μm, etc., and the protein rod-like body marker may have a wall thickness of 0.1 to 0.5. Mu.m, for example, 0.1 μm, 0.15 μm, 0.2 μm, 0.25 μm, 0.3 μm, 5 μm, etc.
In the present invention, the protein rod markers are distributed mainly in the high-valent nuclear PO region, secondarily in the VM nuclear region, and the balance in other regions.
In the present invention, the other region includes any one or a combination of at least two of a lateral posterior thalamus nucleus, a thalamus dorsal nucleus or a thalamus ventral posterior nucleus.
In the present invention, the distribution amount of the protein rod-like marker in the high-valent core PO region is 88 to 92% (for example, 88%, 88.5%, 89%, 89.5%, 90%, 90.5%, 91%, 92% and the like), the distribution amount of the protein rod-like marker in the VM core region is 7 to 9% (for example, 7%, 7.5%, 8%, 8.5%, 9% and the like), and the balance is distributed in other regions, based on 100% of the mass of the protein rod-like marker.
In the invention, PO is a high-order nucleus of thalamus, PO neurons project to the 1 st layer and fifth layer neurons of the primary somatosensory cortex (S1), and simultaneously receive feedback projections of the primary somatosensory cortex neurons, and the PO neurons are relay stations of the paralemniscal somatosensory pathway. We demonstrate that PO intracore Coronin2B rod neurons establish synaptic connections with S1BF neurons of the primary somatosensory cortex. Further we found that the knockout of Coronin2B showed a clear somatosensory disturbance of the sense of touch in the transgenic mice. The Coronin2B rod-shaped structure can be used for developing the detection basis of somatosensory disorder diseases (autism, social disorder and the like). The Coronin2B rod-shaped structure is suggested to regulate and control somatosensory information transmission of the PO neurons. It is therefore important to fully understand the organization of the rod-like structure of Coronin 2B.
In the present invention, the sprouting structure of the protein rod marker appears in the PO nucleus beginning at 2-3 weeks of age in the mouse, appears as weak and dispersed aggregation spots, and has a length of 0.1-3 μm (for example, 0.1 μm, 0.5 μm, 1 μm, 1.5 μm, 2 μm, 2.5 μm, 3 μm, etc.); the development structure of the protein rod marker starts to evolve into a rod-shaped embryonic form with the length of 1-5 μm (for example, 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, etc.) after 2 weeks of age of the mouse; the distribution amount of the protein rod-shaped body markers in the PO area of the high-valence nucleus is 88-92% after 8 weeks of age of the mice, and the protein rod-shaped body markers are in a hollow rod-shaped structure and have a final length of 5-10 mu m (for example, 5 mu m, 6 mu m, 7 mu m, 8 mu m, 9 mu m, 10 mu m and the like); decay of the protein rod markers several of the protein rod markers, which account for 88% or more of the distribution in the high priced nuclear PO region, are shortened to a punctiform structure after 24 weeks of age in mice.
In a second aspect, the present invention provides a method for detecting a protein rod marker according to the first aspect, the method comprising the steps of:
(1) Detecting adult mouse brain tissues by an antibody immunofluorescence detection method, and positioning the distribution nuclear region of the protein rod-shaped body marker;
(2) Through behavioral detection of Coronin2B knockout mice, judging whether somatosensory disorders of the mice occur or not;
(3) The structure of the mouse protein rod markers in the PO region at different age stages was monitored.
Immunofluorescence detection of the adult mouse brain tissue with Coronin2B antibody it was found that the rod-like structure of Coronin2B was mostly located within the PO nucleus and VM nucleus of the mouse thalamus. Somatosensory behavior (new object recognition, three-box social interaction) detection is carried out on Coronin2B knockout mice, and the somatosensory disorder is found. By examining the rod-like structure of Coronin2B in mice of different ages, we found that it was correlated with the age of mice and could be developed as a tool for age prediction. We also found that it locates abnormalities early (2 months of age) in Alzheimer's disease mice (APP/PS 1) and is different from normal mice throughout the phase of AD, suggesting that this structure may serve as a physiological index and early biomarker for AD.
In a third aspect, the present invention provides the use of a protein rod marker according to the first aspect as a marker of thalamus somatosensory related nuclear area, as a detection basis for somatosensory disorders, as a detection basis for age-related disorders, as a physiological index for alzheimer's disease, as an early biomarker for alzheimer's disease.
In a fourth aspect, the present invention provides the use of a protein rod marker according to the first aspect for the preparation of a marker or detection criteria for diagnosis and treatment of a disease associated with somatosensory neurological disorders.
In the study of the present invention, the knockout of Coronin2B clearly revealed that mice developed somatosensory and cognitive disorders. Thalamus PO nuclear excitability and cortical excitability imbalance in Coronin2B knockout mice are also seen during induction of somatosensory events, indicating that Coronin2B knockout affects the neuronal activity of somatosensory loops. Furthermore, the present invention compares the distribution of the thalamus three somatosensory areas to find a high overlap with the distribution of Coronin2B rod, and we also confirm that the knockout of Coronin2B is indeed associated with somatosensory disorders. These grounds make us believe that there is a great possibility of new somatosensory divided regions. Coronin2B rod is likely to act as a very simple visual somatosensory marker landmark and can be used as a marker of thalamus somatosensory related nuclear areas.
Compared with the prior art, the invention has the following beneficial effects:
the invention aims to provide a protein rod-shaped structure and application thereof in somatosensory nerve disorder. The protein rod-shaped body structure is related to maintaining normal physiological functions of neurons, can influence somatosensory nerve information transmission functions, and can provide markers or detection standards for diagnosis and treatment of diseases related to somatosensory nerve disorders. The rod-like structure is related to development, and the shape and the number of the rod-like structure are different in different age groups, so that the rod-like structure can also be developed into an age development disorder disease detection object. Meanwhile, the kit is abnormal in the senile dementia model, so that the kit can be used as a physiological index and an early biomarker of neurodegenerative diseases such as senile dementia.
Drawings
FIG. 1 is a graph of the distribution nuclear region of protein rod markers (Coronin 2B rod structure).
FIG. 2A is a side view of a protein rod marker (Coronin 2B rod structure, 5 μm) under a confocal microscope.
FIG. 2B is a cross-sectional view of a protein rod marker (Coronin 2B rod structure, 2 μm) under a confocal microscope.
FIG. 3 is a development chart of a marker (Coronin 2B rod structure) of a mouse brain protein rod at different age stages.
FIG. 4 is a diagram showing an abnormality observation of a protein rod-like body marker (Coronin 2B rod-like structure) in AD mice.
FIG. 5 is a graph showing the length development of the marker (Coronin 2B rod structure) of the protein rod in the brain of mice of different ages.
FIG. 6 is a graph showing the development of the levels of the marker (Coronin 2B rod structure) in the brain of mice of different ages.
Fig. 7A is a graph showing the time-of-investigation of mice before and after knockout of Coronin 2B.
Fig. 7B is a graph showing the change in discrimination index of mice before and after knockout of Coronin 2B.
Fig. 8A is a graph of social time change in mice before and after knockout of Coronin 2B.
Fig. 8B is a graph of social novelty time change of mice before and after Coronin2B knockout.
Detailed Description
The technical scheme of the invention is further described by the following specific embodiments. It will be apparent to those skilled in the art that the examples are merely to aid in understanding the invention and are not to be construed as a specific limitation thereof.
Example 1
The embodiment provides a localization method of a protein rod marker, which comprises the following steps: immunofluorescence detection of adult mouse brain tissue by Coronin2B antibody;
immunofluorescence staining step: a suitable amount of blocking solution was added to a 30 μm mouse brain slice to permeabilize and block the cells (blocking solution: 10% BSA,4% sheep serum, and 0.4% Triton-X100 were added sequentially to 1mL PBS), and the mixture was reacted at room temperature for 20 minutes. Primary antibodies were diluted in PBS containing 10% bsa,1% sheep serum and 0.2% triton-X100 at a certain ratio (see appendix), and then cells were incubated overnight at 4 degrees after adding the primary antibody dilution. The next day, after washing off the primary antibody with PBS, the appropriate secondary antibody was selected and diluted in PBS containing 10% bsa,4% sheep serum, 0.2% triton-X100 in proportion (see appendix), and then added to the cell wells for incubation at room temperature for 2 hours. After the PBS washes off the secondary antibody, the tweezers take out the climbing sheet and finally seal the sheet. Protein rod markers (Coronin 2B rod structures) were observed using confocal microscopy (Zeiss LSM 880) taking 10, 20 and 63-fold images.
FIG. 1 is a diagram of the distribution core region of a Coronin2B rod-like structure. As shown in fig. 4, it was found by counting green fluorescent spots that the structure was distributed 90% in the posterior thalamus nucleus (PO), 8% in the ventral medial thalamus nucleus (VM), and 2% in the lateral posterior thalamus nucleus (LP), the medial thalamus nucleus (MD), the posterior thalamus nucleus (VPPC), and the like. PO is the higher order nucleus of the thalamus, PO neurons project onto the 1 st and fifth layer neurons of the primary somatosensory cortex (S1), and also receive feedback projections of the primary somatosensory cortex neurons, being relay stations of the paracentescol somatosensory pathway. We demonstrate that PO intracore Coronin2B rod neurons establish synaptic connections with S1BF neurons of the primary somatosensory cortex.
Example 2
The present embodiment provides a method for observing a protein rod-like body marker, comprising the steps of: protein rod markers (Coronin 2B rod structure) were observed by confocal microscopy and by super resolution (both using Zeiss LSM 880), respectively;
FIG. 2A is a side view of a protein rod marker (Coronin 2B rod structure, 5 μm) under a confocal microscope. FIG. 2B is a cross-sectional view of a protein rod marker (Coronin 2B rod structure, 2 μm) under a confocal microscope. As shown in FIGS. 2A-2B, the Coronin2B rod-like structure of adult mice has a length of about 5-10 μm and an inner diameter of about 1-3 μm and an inner wall of about 0.1-0.5. Mu.m.
Example 3
The embodiment provides a method for detecting a mouse brain protein rod-shaped body marker at different age stages, which specifically comprises the following steps: immunofluorescence staining method for brain slice.
Immunofluorescence staining step: a suitable amount of blocking solution was added to a 30 μm mouse brain slice to permeabilize and block the cells (blocking solution: 10% BSA,4% sheep serum, and 0.4% Triton-X100 were added sequentially to 1mL PBS), and the mixture was reacted at room temperature for 20 minutes. Primary antibodies were diluted in PBS containing 10% bsa,1% sheep serum and 0.2% Triton-X100 at a certain ratio, and then cells were incubated overnight at 4 degrees after adding the primary antibody dilution. The next day, after washing off the primary antibody with PBS, the appropriate secondary antibody was selected and diluted in PBS containing 10% bsa,4% sheep serum, 0.2% triton-X100 in proportion (see appendix), and then added to the cell wells for incubation at room temperature for 2 hours. After the PBS washes off the secondary antibody, the tweezers take out the climbing sheet and finally seal the sheet. Protein rod markers (Coronin 2B rod structures) were observed using confocal microscopy (Zeiss LSM 880) taking 10, 20 and 63-fold images.
FIG. 3 is a development chart of a marker (Coronin 2B rod structure) of a mouse brain protein rod at different age stages. As shown in fig. 3, this structure was found to be related to mouse development. It starts to appear in the PO nucleus around 2 weeks old in mice, presenting weak and dispersed aggregation spots (about 0.1-3 μm in length); after 4 weeks of age, the punctiform structures began to evolve into rod-like embryonic forms (about 1-5 μm in length), and the number began to increase as well; after 8 weeks of age, about mouse adulthood, the rod-like structure of Coronin2B is covered with PO nuclei (about 90% of PO neurons) and the length is maintained at about 5-10 μm; after 24 weeks, the mice had essentially gone into the senium and the rod-like structure of Coronin2B had mostly shortened slowly to a punctate form. These results show that the Coronin2B rod structure undergoes a dynamic process in different physiological states in mice, which we define the 4 stages of sprouting (2 w), development (4 w), maturation (8 w) and decay (24 w). The dynamics of Coronin2B rod shape also indicates the difference of mice in age stage, which means that Coronin2B rod shape body can be developed into means or size for predicting age, and is helpful for detecting and treating age-related barrier diseases.
Example 4
This example provides a protein rod marker study for Alzheimer's Disease (AD), including Mild Cognitive Impairment (MCI) patients, comprising the steps of: the change in the distribution of Coronin2B rod-like structures in thalamus PO nuclei of 2-to 9-month-old APP/PS1 mice was compared on a transgenic mouse model of AD (APP/PS 1 mice);
as shown in fig. 4, the Coronin2B rod shape remained largely punctiform when APP/PS1 mice were 8 weeks old, and did not begin to assemble into a short rod until 3 months of age, but became rapidly shorter until the old age. This shows that in model mice for AD, the growth cycle of Coronin2B rod-like structures is affected (see fig. 2A and 2B). This is likely one of the important factors that lead to cognitive impairment of the environment in AD patients. The Coronin2B rod-shaped structure can be used as an AD physiological index and an early biomarker.
As shown in fig. 5-6, both the length and number density of Coronin2B rod structures in APP/PS1 mice were significantly lower than the normal group levels. When APP/PS1 mice were 8 weeks old, the Coronin2B rod shape remained largely in the punctiform type, and did not begin to assemble into a short rod until 3 months of age, but became rapidly shorter until the old age. This shows that in model mice for AD, the growth cycle of Coronin2B rod-like structures is affected (see fig. 2A and 2B). This is likely one of the important factors that lead to cognitive impairment of the environment in AD patients. The Coronin2B rod-shaped structure can be used as an AD physiological index and an early biomarker.
Example 5
The embodiment provides a detection basis for a Coronin2B rod-shaped structure which can develop into a somatosensory disorder disease (autism, social disorder and the like), and the method comprises the following steps: somatosensory behavior (new object identification, three-box social interaction) detection is carried out on Coronin2B knockout mice, and somatosensory disorder is found; and (3) obtaining the Coronin2B gene whole-body knockout mice by using a CRISPR/Cas9 technology. First we were to obtain mRNA and gRNA of Cas9, which was then microinjected into fertilized eggs of mice to obtain transgenic mice. Whether the genes of the offspring are changed or not is confirmed by sequencing the PCR products. The offspring mice were then mated with normal C57BL/6J mice to obtain F1 generation of Coronin2B knockout strain. The F1 knockout mouse lacks 119 base pairs, so that the frame of the target gene protein is shifted, and the target gene protein is terminated in advance, so that a mutant protein of 59 amino acids is theoretically generated; since the translation of the target gene is terminated in advance, the Nonsense-mediated mRNA decay (NMD) effect is probably triggered, so that mRNA of the target gene is degraded, and the gene function is lost.
As shown in fig. 7A-7B, we examined the ability of Coronin2B to discriminate between new objects using this paradigm of new object recognition, and the results showed that the Coronin2B knockout mice were significantly less interested in new objects than wild type mice, indicating that the mice were less exploring for new objects after Coronin2B knockout, and were also less able to discriminate between new objects than normal.
As shown in fig. 8A-8B, the three-box social behavior test results showed that the mouse knocked out with Coronin2B showed very low social activity, indicating that the Coronin2B knockout was problematic in the somatosensory of a beard touch.
In summary, the present invention provides for the first time a novel protein rod structure (Coronin 2B rod structure) in the thalamus PO region; and the Coronin2B rod-shaped structure is related to age development and can be used as an age prediction tool and a developmental disorder detection object. In addition, the rod-shaped structure of the oronin2B is related to AD development and can be used as a physiological index and an early biomarker of neurodegenerative diseases. In particular, the Coronin2B rod-shaped structure can influence somatosensory nerve information transmission function, and can provide markers or detection standards for diagnosis and treatment of diseases related to somatosensory nerve disorder.
The applicant states that the protein rod markers of the present invention and their use are illustrated by the examples described above, but the invention is not limited to, i.e. does not necessarily depend on, the process steps described above. It should be apparent to those skilled in the art that any modification of the present invention, equivalent substitution of selected raw materials, addition of auxiliary components, selection of specific modes, etc. fall within the scope of the present invention and the scope of disclosure.
Claims (10)
1. A protein rod marker, wherein the protein rod marker has a hollow rod-like structure and the protein rod marker is present within excitatory neuronal cell bodies.
2. The protein rod marker of claim 1, wherein the final length of the protein rod marker is 5-10 μιη.
3. A protein rod marker according to claim 1 or 2, wherein the cross section of the protein rod marker is irregularly rounded, the inner diameter of the protein rod marker is 1-3 μm, and the wall thickness of the protein rod marker is 0.1-0.5 μm.
4. The protein rod marker of any one of claims 1-4, wherein the protein rod marker is distributed primarily within the high valent core PO region, secondarily within the VM core region, and the balance being the other regions.
5. The protein rod marker of claim 4, wherein the additional region comprises any one or a combination of at least two of the lateral posterior thalamus nucleus, the dorsolateral thalamus nucleus, or the retrothalamus nucleus.
6. The protein rod marker according to claim 4 or 5, wherein the distribution amount of the protein rod marker in the high-valent core PO region is 88 to 92%, the distribution amount of the protein rod marker in the VM core region is 7 to 9%, and the balance is distributed in other regions, based on 100% of the mass of the protein rod marker.
7. The protein rod marker of any one of claims 1-6, wherein the sprouting structure of the protein rod marker appears in the PO nucleus beginning 2-3 weeks old in mice, appears as weak and dispersed aggregation spots, and has a length of 0.1-3 μιη; after 2 weeks of age of the mice, the development structure of the protein rod-shaped body marker starts to evolve into a rod-shaped embryonic form, and the length of the protein rod-shaped body marker is 1-5 mu m; after 8 weeks of age of the mice, the distribution amount of the protein rod-shaped body markers in the high-valence nuclear PO area is 88-92%, and the protein rod-shaped body markers are in a hollow rod-shaped structure and have a final length of 5-10 mu m; decay of the protein rod markers several of the protein rod markers, which account for 88% or more of the distribution in the high priced nuclear PO region, are shortened to a punctiform structure after 24 weeks of age in mice.
8. A method of detecting a protein rod marker according to any one of claims 1 to 7, comprising the steps of:
(1) Detecting adult mouse brain tissues by an antibody immunofluorescence detection method, and positioning the distribution nuclear region of the protein rod-shaped body marker;
(2) Through behavioral detection of Coronin2B knockout mice, judging whether somatosensory disorders of the mice occur or not;
(3) The structure of the mouse protein rod markers in the PO region at different age stages was monitored.
9. Use of a protein rod marker according to any one of claims 1-7 as a marker of thalamus somatosensory related nuclear area, as a detection basis for somatosensory disorders, as a detection basis for age-related disorders, as a physiological index for alzheimer's disease, as an early biomarker for alzheimer's disease.
10. Use of a protein rod marker according to any one of claims 1-7 for the preparation of a marker or detection standard for diagnosis and treatment of a disease associated with somatosensory neurological disorders.
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| PCT/CN2022/101500 WO2023206773A1 (en) | 2022-04-25 | 2022-06-27 | Protein rod-shaped body marker and use thereof |
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