Mitochondria are structures within the cell that convert energy from food into energy the cell can use. Each cell contains hundreds to thousands of mitochondria. Although most DNA is found inside the cells nucleus, mitochondria also contain a small amount of DNA, known as mitochondrial DNA.
In the early 2000s, researchers realized that short sections of mitochondrial DNA encode small (less than 100 amino acids long), biologically active proteins, now referred to as mitochondrial microproteins. The first mitochondrial microprotein to be discovered was called humanin.
There is growing evidence that humanin and other similar mitochondrial microproteins play a role in several age-related conditions, including Alzheimers disease.
Alzheimers disease is the most common type of dementia, characterized by progressive mental deterioration. According to the CDC, as many as 5.8 million Americans were living with Alzheimers disease in 2020.
The Cohen Laboratory at the University of Southern California (USC), one of the three laboratories that independently discovered humanin in 2003, has discovered a new microprotein connected to the risk of Alzheimers disease.
Their latest research, published in the journal of Molecular Psychiatry, revealed that a mutation in the newly discovered SHMOOSE microprotein is associated with a higher risk for Alzheimers disease across four cohorts. According to the researchers, nearly 1 in 4 individuals with European ancestry have the mutated version of the protein.
Dr. Pinchas Cohen, professor of gerontology, medicine, and biological sciences and senior author of the study, told Medical News Today:
The implications are not immediate, but we believe that [relatively soon], the SHMOOSE SNP [single nucleotide polymorphism] genetic variant that is found in over 20% of Europeans may guide both the classification of individuals that are at risk for Alzheimers that may benefit from certain preventive measures and also could inform the selection of medical interventions that will become available in the near future. A bit further ahead, SHMOOSE [protein] analogues may become available as therapeutics for individuals who carry the SNP and develop dementia, in a precision medicine approach.
Brendan Miller, Ph.D., first author of the study, studied mitochondrial DNA sequences from the Alzheimers Disease Neuroimaging Initiative (ADNI) database, searching for small variations in the genes called single nucleotide polymorphisms or SNPs. He found that a mutation in one particular mitochondrial SNP (rs2853499) was associated with a greater risk of Alzheimers disease and brain atrophy.
Dr. Miller and his colleagues then discovered that the mutated SNP causes a change in a mitochondrial microprotein, which they called SHMOOSE. The researchers used a technique called immunoprecipitation to isolate the SHMOOSE microprotein from the mitochondria of nerve cells.
When they analyzed this sample using mass spectrometry, they detected and identified two unique protein fragments from the SHMOOSE microprotein. The researchers reported that this is the first unique mass spectrometry-based detection of a mitochondrial-encoded microprotein to date.
Having identified a microprotein associated with a higher risk of Alzheimers disease, the researchers followed up on their discovery by carrying out studies in rats and cell culture experiments.
They found that the SHMOOSE microprotein accumulates in the mitochondria of neurons (nerve cells), where it binds to the inner mitochondrial membrane protein mitofilin. The SHMOOSE microprotein appears to act on the brain by influencing mitochondrial gene expression and boosting mitochondrial oxygen consumption. The researchers noted that mutated SHMOOSE microprotein was less effective at boosting oxygen consumption and impacted gene expression differently.
Dysregulated mitochondrial associated brain energetics is one of the multiple pathways thought to be important for Alzheimers disease, Andrew Saykin, PsyD, ABCN, Professor and Director of the Center for Neuroimaging and Indiana Alzheimers Disease Research Center, told MNT.
George Perry, Ph.D., Professor and Semmes Foundation Distinguished University Chair in Neurobiology at the University of Texas at San Antonio, told MNT that this study is very important as it links risk of [Alzheimers disease] to cellular metabolism. There are numerous cell biology and biochemical studies that highlight this [] and finding genetic data further support[s] this view.
Dr. Saykin observed that with further development and validation there could be implications of this and other microproteins for early detection, longitudinal monitoring, and potentially for therapeutic targeting.
MNT also discussed the studys findings with Tal Nuriel, Ph.D., Assistant Professor of Pathology and Cell Biology at Columbia University Irving Medical Center. Dr. Nuriel told MNT that most Alzheimers disease-related gene mutations discovered in the past are either very rare variants or common variants that confer a very small risk.
He said the mutation, or variant, in the SHMOOSE microprotein appears to confer a moderate risk for Alzheimers disease and is relatively common in the population and [this] alone makes it interesting.
Dr. Nuriel added that the fact that this is a microprotein that can theoretically be administered as a therapeutic agent is valuable. He cautioned that there will be a very long road ahead before any therapy derived from this microprotein could become a reality. Importantly, its unclear whether this SHMOOSE microprotein would enter the brain if given subcutaneously or intravenously. And if it doesnt enter the brain, this would greatly limit its ability to be used therapeutically.
When asked about the next step in the research following this discovery, Dr. Cohen told MNT, Our immediate plan is to treat mice that have been engineered to develop Alzheimers disease with SHMOOSE over several months and assess the improvement in their symptoms and performance. We will also work on developing longer acting analogues of the pep[t]ide.
The researchers noted in the study that SHMOOSE is yet another microprotein of a growing number that modify mitochondrial biology. According to a recent review, thousands of DNA sequences with microprotein-coding potential are currently unverified or functionally uncharacterized.
Read the rest here:
Alzheimer's disease risk linked to newly discovered protein mutation - Medical News Today
- Gene Therapy for Genetic Disease: The Long and Winding Road [Last Updated On: August 17th, 2024] [Originally Added On: October 10th, 2011]
- Gene Doping: Super Athletes in 2008 Beijing Olympics - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 14th, 2011]
- The 3 Rs of DNA: Molecules to Medicine - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 15th, 2011]
- BIT 3.1 Entrez Gene - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 15th, 2011]
- Professor Ian Everall - Gene expression in schizophrenia - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 16th, 2011]
- Gene Therapy Promising Treatment (Part 2 of 4) - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 16th, 2011]
- Cancer Research @ NC State's Centennial Biomedical Campus - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 16th, 2011]
- Gene Therapy Promising Treatment (Part 1 of 1) - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 19th, 2011]
- HiTech_U3L3_Biotech in Medicine - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 19th, 2011]
- Sri Sathya Sai Medical Camps Worldwide - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 20th, 2011]
- Dr. Joseph M. DeSimone: 2008 Winner, $500000 Lemelson-MIT Prize - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 21st, 2011]
- Non-Hodgkin's Lymphoma Cancer Survivor Testimony - (Sanoviv Medical Institute) - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 22nd, 2011]
- Vaccines: Medicine for the Healthy - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 24th, 2011]
- For Your Health - Health Care Informatics - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 24th, 2011]
- A Century of Stem Cells - Johns Hopkins Medicine - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 24th, 2011]
- Functional Repair of Human Donor Lung by IL-10 Gene Therapy (EX VIVO Lung) - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 25th, 2011]
- Science Talk: Vaccine Made With Synthetic Gene Protects Against Deadly Pneumonia - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 25th, 2011]
- Health Matters: Family Medicine - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 26th, 2011]
- Dr. Jeffrey Myers Explains Genetic Variations in Head and Neck Cancer - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 27th, 2011]
- The Emerging Network of Data for Understanding the Interactions of Genes and Drugs - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 27th, 2011]
- Burzynski_ Cancer Is Serious Business Part 4/8. wmv - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 27th, 2011]
- Pt2: Do you understand the new genetics? Maybe you don't have that gene! - Andrew Shelling - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 27th, 2011]
- Alien Genetic Takeover of Humanity! - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 27th, 2011]
- Burzynski | 2-DVD Set Extended Edition Montage Preview of New Material | Cancer Is Serious Business - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 27th, 2011]
- Genes, Genomes and the Future of Medicine - Richard Lifton, MD, Ph.D. - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 27th, 2011]
- Burzynski The Movie ~ Cancer Is Serious Business ~ High Quality - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 27th, 2011]
- Designing Life for Mars Colonization (Brainstorm Ep20) - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 27th, 2011]
- Dedication Event: Santa Monica UCLA Medical Center [Last Updated On: August 17th, 2024] [Originally Added On: October 27th, 2011]
- DR. Burzynski The Movie - Cancer Is Serious Business (PT.1) - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 27th, 2011]
- burzy - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 28th, 2011]
- Alien Genetic Takeover: The End of Humanity - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 28th, 2011]
- Burzynski_ Cancer Is Serious Business Part 1/8 .wmv - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 28th, 2011]
- Mike Schmidt - ECMO Patient - Penn State Hershey Medical Center - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 28th, 2011]
- Disrupting the HIV Virus (Brainstorm Ep24) - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 28th, 2011]
- Diagnosis and Treatment of Hepatorenal Syndrome - Moving Targets? - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 28th, 2011]
- Big Bucks, Big Pharma: Marketing Disease and Pushing Drugs - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 28th, 2011]
- Roles of RNA in Gene Regulation - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 28th, 2011]
- Diatom PCR Colony Screen - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 28th, 2011]
- Kleanthis G. Xanthopoulos, Ph.D., CEO, Regulus, talking on the impact of microRNA medicines - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 28th, 2011]
- Burzynski_ Cancer Is Serious Business Part 2/8 .wmv - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 28th, 2011]
- Sickle Cell Anemia: Stem Cell Gene Therapy - A Patient's Perspective - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 29th, 2011]
- Gene-based lung cancer treatment video - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 29th, 2011]
- HIV Resistant Genes...Rhesus Negative, Excess PK [Last Updated On: August 17th, 2024] [Originally Added On: October 29th, 2011]
- Futures in Biotech 83: Bioinformatics: Essential Gene names Skewed in a Network of Blame - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 29th, 2011]
- Keeping Blood Young, Fighting Sickle Cells (Brainstorm Ep28 - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 31st, 2011]
- News@Northwestern - NUGENE - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 31st, 2011]
- UK Medical Student Mary Burchett's Research is Personal - Video [Last Updated On: August 17th, 2024] [Originally Added On: October 31st, 2011]
- Cannabis 4 Crohn's: 2 Years As Medical Marijuana Patient, Dr Mind Bender [Last Updated On: August 17th, 2024] [Originally Added On: November 8th, 2011]
- Medical Haptical Robot for the Eye - Eye-Rhas, - TU Eindhoven - Video [Last Updated On: August 17th, 2024] [Originally Added On: November 8th, 2011]
- The Ghost in Your Genes - Horizon - BBC - Video [Last Updated On: August 17th, 2024] [Originally Added On: November 9th, 2011]
- The Ghost in Your Genes - BBC Horizon - Video [Last Updated On: August 17th, 2024] [Originally Added On: November 13th, 2011]
- Burzynski: Cancer Is Serious Business (Trailer) - Video [Last Updated On: August 17th, 2024] [Originally Added On: November 16th, 2011]
- Genes, Ancestry, and Personalized Medicine with Dr. Michael Kane - Interview Part 1.mp4 - Video [Last Updated On: August 17th, 2024] [Originally Added On: November 25th, 2011]
- The Suicide Gene - Video [Last Updated On: August 17th, 2024] [Originally Added On: November 29th, 2011]
- Ard Louis on Dawkins and Selfish Genes - Video [Last Updated On: August 17th, 2024] [Originally Added On: November 30th, 2011]
- TEDxLex - Dr. Alicia L. Bertone - Gene Jockeying for a Win in Regenerative Medicine.mp4 - Video [Last Updated On: August 17th, 2024] [Originally Added On: December 3rd, 2011]
- Introduction to Gene Network - Video [Last Updated On: August 17th, 2024] [Originally Added On: December 7th, 2011]
- The demise of a dogma. The deaf somatic gene listens - Video [Last Updated On: August 17th, 2024] [Originally Added On: December 7th, 2011]
- Future of health care, hospitals, medicine and wellbeing - by Dr Patrick Dixon - Video [Last Updated On: August 17th, 2024] [Originally Added On: December 8th, 2011]
- Electro-Medicine : Biological Physics : Neurological Research Advancements - Video [Last Updated On: August 17th, 2024] [Originally Added On: December 12th, 2011]
- Haemophilia gene therapy breakthrough - Video [Last Updated On: August 17th, 2024] [Originally Added On: December 15th, 2011]
- Duke researchers: Gene discovery explains how fruit flies retreat from heat - Video [Last Updated On: August 17th, 2024] [Originally Added On: December 16th, 2011]
- Focus on Nikolaus Rajewsky - Video [Last Updated On: August 17th, 2024] [Originally Added On: December 18th, 2011]
- Deadly Monopolies Medical Ethicist Harriet Washington on How Firms are Taking Over Life Itself - Video [Last Updated On: August 17th, 2024] [Originally Added On: December 23rd, 2011]
- Open fetal surgery: past, present and future - Video [Last Updated On: August 17th, 2024] [Originally Added On: December 23rd, 2011]
- The Human Genome and Individualized Medicine - David Valle, MD - Video [Last Updated On: August 17th, 2024] [Originally Added On: January 14th, 2012]
- Environmental Contributors to Autism Spectrum Disorders - Video [Last Updated On: August 17th, 2024] [Originally Added On: January 20th, 2012]
- When Cancer Runs in the Family - Video [Last Updated On: August 17th, 2024] [Originally Added On: January 20th, 2012]
- Genome Enabled Electronic Medical Record (GenE EMR) - William Knaus - Video [Last Updated On: August 17th, 2024] [Originally Added On: January 22nd, 2012]
- Nuvigil withdrawal - Video [Last Updated On: August 17th, 2024] [Originally Added On: January 23rd, 2012]
- Cancer Cure Documentary - Dr. Burzynski Antineoplaston Therapy - Video [Last Updated On: August 17th, 2024] [Originally Added On: January 26th, 2012]
- Next Generation Cancer Gene Sequencing for Clinically Actionable Mutations - Video [Last Updated On: August 17th, 2024] [Originally Added On: January 26th, 2012]
- Fibrocell Science, Inc. Announces Recognition for LAVIV™ (azficel-T) at The 2012 Cell & Gene Therapy Forum, Washington ... [Last Updated On: August 17th, 2024] [Originally Added On: January 31st, 2012]
- Gene Mutation Linked to Inappropriate Lipid Buildup in Liver [Last Updated On: August 17th, 2024] [Originally Added On: February 1st, 2012]
- 'Goldilocks' gene could determine best treatment for tuberculosis patients [Last Updated On: August 17th, 2024] [Originally Added On: February 3rd, 2012]
- James Wilson, MD, Ph.D., on Gene Therapy as a Disruptive Technology - Video [Last Updated On: August 17th, 2024] [Originally Added On: February 3rd, 2012]
- 'Goldilocks' gene used to find drug treatment that is 'just right' for TB patients [Last Updated On: August 17th, 2024] [Originally Added On: February 4th, 2012]
- Gene therapy, a totally Italian success - Video [Last Updated On: August 17th, 2024] [Originally Added On: February 4th, 2012]
- Electro-Medicine : Neurons function revealed - Video [Last Updated On: August 17th, 2024] [Originally Added On: February 4th, 2012]
- Gene mutation discovery sparks hope for effective endometriosis screening [Last Updated On: August 17th, 2024] [Originally Added On: February 7th, 2012]