노벨상
노벨상 업적에 투자하기 – 자가포식
노벨상 역사
The Nobel Prize is the most prestigious award in the scientific world. It was created according to 알프레드 노벨의 유언 to give a prize “전년도에 인류에게 가장 큰 혜택을 제공한 사람들에게” in physics, chemistry, physiology or medicine, literature, and peace.
A sixth prize would be later on created for economic sciences by the Swedish central bank, officially called the Prize in Economic Sciences, often better known as the Nobel Prize in Economics.
The decision of who to attribute the prize to belongs to multiple Swedish academic institutions.
유산에 대한 우려
The decision to create the Nobel Prize came to Alfred Nobel after he read his own obituary, following a mistake by a French newspaper that misunderstood the news of his brother’s death. Titled “The Merchant of Death Is Dead”, the French article hammered Nobel for his invention of smokeless explosives, of which dynamite was the most famous one.
His inventions were very influential in shaping modern warfare, and Nobel purchased a massive iron and steel mill to turn it into a major armaments manufacturer. As he was first a chemist, engineer, and inventor, Nobel realized that he did not want his legacy to be one of a man remembered to have made a fortune over war and the death of others.
노벨상
These days, Nobel’s Fortune is stored in a fund invested to generate income to finance the Nobel Foundation and the gold-plated green gold medal, diploma, and monetary award of 11 million SEK (around $1M) attributed to the winners.
출처: Britannica
Often, the Nobel Prize money is divided between several winners, especially in scientific fields where it is common for 2 or 3 leading figures to contribute together or in parallel to a groundbreaking discovery.
Over the years, the Nobel Prize became THE scientific prize, trying to strike a balance between theoretical and very practical discoveries. It has rewarded achievements that built the foundations of the modern world, like 방사능, 항생제, X-레이, or PCR, as well as fundamental science like the 태양의 에너지 원천, the 전자 전하, 원자 구조, or 초유동성.
‘자가 섭식’ 재활용
When progress in microscopy allowed us to learn about the inner workings of complex cells, scientists discovered that they contained many sub-units, each performing a special function.
This discovery was rewarded by 1974년 생리학·의학 노벨상, in part to the Belgian scientist Christian de Duve for the discovery of the lysosome.
Lysosomes are specific structures dedicated to digest/recycle components of the cells. This way, a no-longer-wanted or damaged part of the cell can be destroyed safely and its components reused.
It can also be a reaction to a lack of resources, with the cell consuming some of its components to keep working.
출처: Frontiers
Progressively, they discovered that lysosomes can absorb and recycle not only smaller components but entire parts of the cell like whole organelles (ribosome, mitochondria, etc.).
De Duve investigated this process and discovered a dedicated type of vesicle existed to transport what was to be recycled into the lysosome.
De Duve calls this process autophagy, which comes from the Greek words auto-, meaning “self,” and phagein, meaning “to eat.” And the vesicles involved would be called autophagosomes.
출처: Nobel Prize
Autophagy was clearly a very important cellular mechanism, preserved among a wide range of organisms throughout evolution, from amoebas to insects, frogs, and mammals.
However, how this process actually worked stayed a mystery. At least until clever analytical methods were invented by 오오스미 요시노리, the winner of the 2016년 의학 노벨상, for his discovery of autophagy mechanisms.
출처: Nobel Prize
자가포식소 탐지
Yoshinori Ohsumi, when starting to direct his own lab in 1988, went on to focus on vacuole, the cellular organ equivalent to the human lysosome in microorganisms and plant cells.
His primary model was yeast, mostly because it was easier to grow and study yeast than more complex cells. The yeast genome would also be elucidated much sooner than the human genome and was easier to modify genetically.
However, yeasts’ internal structures are difficult to distinguish on a microscope, and it was not clear at the time if autophagy was a mechanism present in yeast.
To elucidate it, Ohsumi created mutant yeast that lacked the genes for the degradation enzyme in the vacuole. The idea was that if the vacuole could not degrade absorbed components, the still theoretical yeast’s autophagosomes would pile up in the cell.
To make the results more clear, Ohsumi also starved the yeasts, forcing them into an intense autophagy activity. The results were almost instantaneous, with a massive accumulation of autophagosomes in the yeast cells easy to spot using simple microscopy.
출처: Nobel Prize
자가포식소 유전자 탐색
Now armed with an easy-to-analyze model to create abundant autophagosomes, Ohsumi would go hunting for the genes responsible for these structures.
To do so, he exposed his yeast to a chemical that created mutations and then induced autophagy. So when one gene responsible for autophagosome was damaged, the process would break, and he could find the mutation and the gene in question.
While somewhat simple in theory, this was a complex affair in practice, and took a lot of work to identify 15 different genes responsible for autophagosome in yeasts.
These genes would be first named APGI-1 to APGI-15, and later on, renamed ATG genes for all autophagy-related genes.
자가포식소 유전자 기능
Ohsumi would also look at these genes and the corresponding proteins and elucidate their biochemical functions.
He would find a complex regulation process: First initiated by a stress signal (TOR), which activates a regulatory complex, activating another protein complex, which then forms the autophagosome vesicles.
출처: Nobel Prize
효모에서 포유류로 확장
Now knowing the genes responsible for autophagy, Ohsumi’s team could go find the equivalent in mammals. Interestingly, they found that in mice, deficiency in the Atg5 gene would cause the mice to be unable to cope with the starvation that precedes feeding and die.
This would be the first indication of how important autophagy and autophagosomes are in all organisms and not just in yeast.
자가포식의 다양한 기능
Further research by Ohsumi and many other scientists would demonstrate that autophagy plays a vital role in response to starvation and other types of stress, as it provides the cell quickly with the energy and building blocks it needs.
It is also responsible for protection against infections, with autophagy able to eliminate invading intracellular bacteria and viruses (xenophagy).
Autophagy would later be proven to contribute to embryo development and cell differentiation.
Cells also use autophagy to eliminate damaged proteins and organelles, a quality control mechanism critical for counteracting the negative consequences of aging. Autophagy is also a key factor in the origin of cancer, with many cancer cells mutating due to damaged mitochondria or other subcellular components.
출처: Nobel Prize
Over time, autophagy became one of the most studied cellular mechanisms, with an explosion in the number of publications after the year 2000.
출처: Nobel Prize
자가포식 관련 질병
With autophagy at the center of so many vital parts of cellular biochemistry and cell survival/maintenance, it is not surprising that problems in autophagy can be the cause of diseases. Alternatively, activation of autophagy could provide a cure for many other diseases.
Deregulation of autophagy has been linked to:
- Human breast and ovarian cancer, with mutation to the BECN1 gene (homolog to yeasts’ ATG6) in a large portion of these cancers.
- Many other mutations or changes in the expression of autophagy genes have been linked to cancer in the liver, skin, kidney, lung, colon, etc.
- Genetic mutations in humans that impair autophagy can cause brain malformations, developmental delay, intellectual disability, epilepsy, movement disorders, and neurodegeneration.
- In animal models, loss of autophagy can cause neurodegeneration, and activation of autophagy can reduce the toxicity of protein aggregates, believed to be a key root cause of Parkinson’s and Alzheimer’s diseases.
- Enhancing autophagy could help treat diabetes (autophagy is inhibited by high glucose levels).
- Autophagy of mitochondria has been linked in complex ways to cardiac arrest, heart failure risks, and progression of cardiomyopathy.
겉보기에 관련 없어 보이는 다양한 질병들이 모두 근본적인 문제, 즉 세포 쓰레기의 축적을 공유합니다.
간에 지방이 축적되면 비알코올성 지방간 질환이 발생합니다. 또한 독성 분자는 희귀 유전 효소 결핍증에서 대량으로 축적됩니다.
자가포식 약물
Activation of autophagy has become an entire field of medical research, considering how many diseases are linked to impaired autophagic functions.
However, the first tries did not really bear fruits, with a focus on inhibiting autophagy in cancer that appears to use autophagy to its benefit. Slow progress dampened investors’ enthusiasm.
A more promising option might be to stimulate autophagy to treat other diseases instead.
약리학적 자가포식 활성화는 일반적으로 포유류 라파마이신 표적(mTOR) 효소 복합체 1(mTORC1)의 키네이스 활성을 차단함으로써 달성됩니다.
자가포식에 투자하기
Autophagy is a very promising field of biotech research thanks to its importance in maintaining proper cellular functions. However, it can also be a complex target for drugs, for the very reason that it is so complex and multifunctional.
It is nevertheless a method likely to bear fruits in solving so far incurable autophagy-linked diseases like Alzheimer’s or Parkinson’s.
You can invest in autophagy companies through many brokers, and you can find here, on securities.io, our recommendations for the best brokers in the USA, Canada, Australia, the UK, as well as many other countries.
If you are not interested in autophagy companies, you can also look into biotech ETFs like WisdomTree BioRevolution UCITS ETF (WBIO), VanEck Biotech ETF (BBH), or First Trust NYSE Arca Biotechnology Index Fund (FBT) which will provide a more diversified exposure to capitalize on the growing biotech economy.
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자가포식 기업
1. Cognition Therapeutics
(CGTX )
Cognition is a biotech company focused on neurodegenerative diseases.
The company is notably targeting amyloid beta oligomers, agglomerates made of proteins that are linked to Alzheimer’s disease.
The amyloid proteins have proven very resistant to treatment, with only one approved treatment (Aducanumab) despite 35 years of research. 제조사 바이오젠은 2021년 승인 이후 2024년에 해당 약물을 중단할 예정입니다.
Cognition Therapeutics is attacking amyloid beta oligomers instead of amyloid plaque, thanks to recent evidence that the oligomers are the actually most neurotoxic form of amyloid beta protein.
This provides the company with a new target untested by previous experimental therapies.
출처: Cognition Therapeutics
뇌와 망막 세포에서 발견되는 시그마-2 수용체 복합체는 뇌 신경망의 ‘청소부’ 역할을 하며, 알츠하이머병, 루이소체 치매, 건성 연령 관련 황반변성(AMD)과 같은 노화 관련 질환의 주요 경로를 조절하는 것으로 여겨집니다.
So the company uses sigma-2 modulators that can restore critical damage responses like protein trafficking and autophagy that are impaired in neurodegenerative diseases.
실험적 시그마-2 수용체 변조제의 인비트로 연구는 Aβ 올리고머가 뉴런에 결합하는 것을 방지하고, 이미 결합된 Aβ 올리고머를 뉴런 수용체에서 분리시키는 능력을 보여주었습니다.
The company is also investigating the potential of its main drug candidate for another form of dementia and an eye disease involving neurodegeneration.
Research in curing Alzheimer’s disease has been an arduous process. At the same time, the aging of the population and the already 6.9 million affected patients in the US alone means that any breakthrough would turn into an instantaneous blockbuster drug.
As Alzheimer’s disease seems intimately linked to protein accumulation that would normally be solved through autophagy, this is a promising prospect for further R&D.
2. ImmuPharma (IMM.L)
ImmuPharma is another biotech company exploring the potential of autophagy in treating diseases.
Its main drug candidate, LP140, is a first-in-class autophagy immunomodulator for the treatment of Lupus.
The drug is already in phase 3 of clinical trials, and pre-clinical data indicate it could be useful for other autophagy-linked diseases.
It is also investigating the antibacterial & antifungal potential of BioAMB, an amphotericin-B variant, a known antifungal molecule.
BioAMB is expected to display much lower kidney toxicity than amphotericin-B and can be administrated with a simple injection instead of an IV.
출처: ImmuPharma
ImmuPharma has an exclusive license and development agreement and trademark agreement for Lupuzor with Avion Pharmaceuticals for its commercialization in the US.
This follows its business model of bringing far enough its candidate drugs, and then “enter into commercial deals with larger companies within the industry that then assume the responsibility to fund and complete the clinical development of each product through to registration and ultimately, market launch.”
