Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: neuroscience

Mitochondria in Alzheimer’s Disease Pathogenesis

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years and above. It causes dementia with memory loss and deterioration in thinking and language skills. AD is characterized by specific pathology resulting from the accumulation in the brain of extracellular plaques of amyloid-β and intracellular tangles of phosphorylated tau. The importance of mitochondrial dysfunction in AD pathogenesis, while previously underrecognized, is now more and more appreciated. Mitochondria are an essential organelle involved in cellular bioenergetics and signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, mitochondrial trafficking, mitochondrial fission, and mitochondrial fusion are dysregulated in the AD brain. Excess fission and fragmentation yield mitochondria with low energy production.

How a chemical reaction triggers brain inflammation in Alzheimer’s disease

The brain has its own immune system, which detects threats and mounts a defense. A growing body of evidence has shown that in Alzheimer’s disease, those immune cells are chronically overactivated, causing inflammation that damages the connections between brain cells.

Now, in a preclinical study using human Alzheimer’s brain cells, scientists at Scripps Research have identified a molecular switch—and potential drug target—responsible for driving that chronic inflammation.

The research, published in Cell Chemical Biology on April 23, 2026, centers on a protein called STING, which normally functions as part of the immune system’s early-warning system. In the brains of people with Alzheimer’s, the team discovered that STING undergoes a chemical modification known as S-nitrosylation (or SNO, a reaction involving sulfur, oxygen and nitrogen) that promotes its overactivation. Blocking this chemical change to STING in a mouse model of the disease decreased neuroinflammation.

Blood and spinal fluid proteins reveal distinct fingerprints of four brain diseases

Researchers at WashU Medicine have uncovered new molecular insights into Alzheimer’s disease, Parkinson’s disease and other forms of dementia by analyzing thousands of proteins in both cerebrospinal fluid and blood plasma. The study, led by Carlos Cruchaga, the Barbara Burton & Reuben Morriss III Professor in the Department of Psychiatry and director of the NeuroGenomics and Informatics Center at WashU Medicine, represents one of the largest and most comprehensive multi-tissue analyses of proteins across multiple neurodegenerative diseases to date. The findings raise the possibility of developing blood tests for earlier and more precise diagnosis of these conditions.

In the study, published March 30 in Neuron, a multi-institutional team of clinicians, neuroscientists and data scientists, steered by Muhammad Ali, an assistant professor of psychiatry at WashU Medicine and first author of the study, analyzed nearly 7,000 proteins in samples of spinal fluid and blood from nearly 6,000 people—including people with neurodegenerative diseases as well as healthy controls—to better understand four major neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, and frontotemporal dementia.

By analyzing these diseases in parallel, the researchers could distinguish both shared and disease‑specific “molecular fingerprints.” Across all four diseases, the protein analysis indicated clear evidence of inflammation, damage to the connections between nerve cells, and changes in the scaffolding around cells known as the extracellular matrix.

Boosting good gut bacteria population through targeted interventions may slow cognitive decline

The origin of neurodegenerative diseases like Alzheimer’s or dementia isn’t limited to the brain. The state of your gut can quietly set off a cycle of chronic, system-wide inflammation that nudges the brain toward cognitive decline. But how does the pathogenesis of a disease that seems purely brain-based begin in the gut—an organ that is mostly busy producing chemicals for digesting food?

It turns out these two entities are linked by the gut-brain axis, a two-way communication superhighway that constantly sends signals between the digestive tract and the central nervous system. It runs on chemical messengers like neurotransmitters and fatty acids, sharing information that shapes our memory, mood, and inflammation triggers.

An analysis of 15 studies involving more than 4,200 participants found that the gut-brain highway can be put to work as a drug-free route to support cognitive health. Tuning the gut microbiota through diet, supplements, or medical interventions such as fecal microbiota transplantation (FMT) can help improve memory, executive function, and overall cognitive performance, particularly in early or mild cases of cognitive impairment.

Frontiers: Year 2020 this gene therapy in mice shows promise for als gene therapy in humans

Gene therapy is an emerging and powerful therapeutic tool to deliver functional genetic material to cells in order to correct a defective gene. During the past decades, several studies have demonstrated the potential of AAV-based gene therapies for the treatment of neurodegenerative diseases. While some clinical studies have failed to demonstrate therapeutic efficacy, the use of AAV as a delivery tool has demonstrated to be safe. Here, we discuss the past, current and future perspectives of gene therapies for neurodegenerative diseases. We also discuss the current advances on the newly emerging RNAi-based gene therapies which has been widely studied in preclinical model and recently also made it to the clinic.

Gene therapy is an emerging therapeutic tool used to deliver functional genetic material to cells in order to correct a defective gene. By delivering a copy of a therapeutic gene to affected cells, the product encoded by that gene [i.e., its messenger RNA (mRNA) and/or proteins] will be continuously synthesized within the cell, utilizing the cell’s own transcriptional and translational machinery (Porada et al., 2013). The main advantage of this technology is that it offers a potentially life-long therapeutic effect without the need for repeated administration. Gene therapy can be used to correct defective genes by introducing a functional copy of the gene, by silencing a mutant allele using RNA interference (RNAi), by introducing a disease-modifying gene, or by using gene-editing technology (Grimm and Kay, 2007; Dow et al., 2015; Saraiva et al., 2016).

Gene therapy vectors can be either viral or non-viral. Different physical and chemical systems can be applied to deliver therapeutic genes to cells without the need of a viral vector. Non-viral vectors have no size limitation for the therapeutic gene, generally have a low immunogenicity risk, and can be produced at relatively low costs (Nayerossadat et al., 2012). However, due to the fact that high therapeutic doses are required when using non-viral technologies, and the resulting gene expression is generally transient, most gene therapies now rely on viral vectors. Numerous viral vector types have been tested in clinic, including vaccinia, measles, vesicular stomatitis virus (VSV), polio, reovirus, adenovirus, lentivirus, γ-retrovirus, herpes simplex virus (HSV) and adeno-associated virus (AAV) (Lundstrom, 2018).

Gene therapy for deafness approved

The world’s first gene therapy for deafness received approval from the U.S. Food and Drug Administration today. The treatment, from biotech company Regeneron, targets hearing loss caused by inherited mutations in the OTOF gene, which encodes otoferlin, a protein that allows the inner ear’s hair cells to sense and transmit sound to the brain. Patients receive a one-time ear injection containing viral vectors that carry a working copy of the OTOF gene into their cells. In a clinical trial, nine of 12 deaf children who initially received the Regeneron therapy gained enough hearing to stop using cochlear implants; three within that group ended up having normal hearing. Although many gene therapies cost $1 million or more, Regeneron said its treatment, called Otarmeni, will be free in the United States.

Eli Lilly & Co. and researchers in China are also developing gene therapies for OTOF mutations, which account for up to 3% of cases of inherited deafness. One U.S.-Chinese team reported in Nature this week that among 24 patients, including some adults, hearing improvements have lasted more than 2 years in some cases, NPR reports. Researchers eventually hope to treat other types of genetic deafness as well, but those attempts face more challenges. For example, for some disorders, it may be necessary to regenerate lost hair cells. In others, targeting the wrong cell type could damage hearing.

Label-free optical imaging enables automated measurement of human white matter microstructure

White matter pathways allow distant parts of the brain to communicate, supporting memory, emotion, and language. One such pathway, the uncinate fasciculus, connects the front of the temporal lobe with regions of the frontal cortex involved in decision-making and social behavior. Despite its importance, little is known about the microscopic structure of this tract in the human brain.

Traditional techniques such as electron microscopy can reveal fine details, but they often fail when applied to postmortem human tissue, which is frequently degraded.

In a study published in Biophotonics Discovery, researchers report a new way to examine white matter structure in postmortem human brains.

Recent Scientific Evidence that Supports Nichols’s Lost Primal Eye Theory of Mind I. Core Premise: The Evolutionary Shift

The Phantom Organ and The “Hard Problem” — I apply MVT to solve David Chalmers’s “Hard Problem” of consciousness-the question of why physical brain processes are accompanied by subjective feelings (qualia).

Nichols’s theory posits that self-referential consciousness and abstract thought in many modern animals are the evolutionary result of the loss of a physical sensory organ: the parietal/pineal eye (the “primal eye”). Nichols maps this transition across three brain states in vertebrate evolution: The E2 State (Finite-State): Early fish, amphibians, and ancestral reptiles (as well as modern “living fossils” like the Tuatara) possessed a functional, light-sensitive median eye on top of their skulls, connected to the pineal gland. This organ directly controlled thermoregulation, circadian rhythms, and basic predator detection in coldblooded (ectothermic) animals. Their brains were “hard-wired,” responding directly to environmental stimuli. The E1 State (Infinite-State): As mammals and birds evolved warmbloodedness (endothermy), external temperature sensing became redundant, and advanced lateral eyes took over visual duties. The primal eye atrophied, leaving behind only the internal pineal gland. Freed from the direct “lock-step” control of the sun, the brain became plastic and self-organising (infinite-state). The E0 State: Some lineages, like certain dinosaurs and modern crocodilians, lost both the median eye and the pineal gland entirely. II. The Phantom Organ and The “Hard Problem” Nichols applies MVT to solve David Chalmers’s “Hard Problem” of consciousness-the question of why physical brain processes are accompanied by subjective feelings (qualia). The Virtual Sensor: Just as an amputee can experience a “phantom limb” because the neural matrix still expects the arm, the E1 mammalian brain experiences a “phantom eye”. The brain was built over millions of years to process a central stream of generic sensory data from the primal eye. Centrally Evoked Mentation: When the physical eye retreated, it left an internal sensory void. The brain compensated by simulating the presence of this lost hub to unscramble data from the other senses. This virtual simulation is the seat of the subjective “I”. III. The Origins of REM Sleep and Dreaming Nichols heavily critiques philosophers like Owen Flanagan, who argue that dreams are useless evolutionary “spandrels” (biological noise). Baseline Architecture: In MVT, Rapid Eye Movement (REM) sleep is the baseline functional state of the new E1 architecture. Because the physical tether to sunlight was severed, the brain uses this “phantom” space to generate internal models.

For the first time, scientists pinpoint the brain cells behind depression

Scientists have identified two specific types of brain cells that behave differently in people with depression, offering a clearer picture of what is happening inside the brain. By analyzing donated brain tissue with advanced genetic tools, the researchers found changes in neurons linked to mood and stress, as well as in immune-related microglia cells. These differences point to disruptions in key brain systems and reinforce that depression is rooted in biology, not just emotions.

/* */