Slowing down neurodegenerative diseases
A healthy human brain contains about 100 billion neurons, or nerve cells — these cells are the cellular basis for all of our memories, thoughts, sensations (e.g., taste), emotions, movements and skills. Neurons quickly receive and process incoming information and transmit “messages” to where they are needed. Long, branching extensions from the cell body of neurons form synapses (i.e., connections) with other neurons. About 100 trillion synapses allow these electrochemical signals to travel rapidly throughout the nervous system.
Neurons are important for relaying messages through electrical impulses and chemical signals between different areas of the brain and between the brain and nervous system. Every reaction, movement, thought and feeling we have every day would be impossible without neurons and their supportive (i.e., glial) cells. In the human brain, there are millions of highly differentiated cells that are specialized to perform certain functions (e.g., sensory neurons, motor neurons, interneurons), depending on where they are located. For example, sensory neurons in our muscles, joints and skin help to communicate pain, temperature and pressure.
In patients with neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD), there is a progressive deterioration or death of neurons in the brain, resulting in a loss of nerve structure and function. Neurodegeneration, or the progressive death of nerve cells, in certain areas of the brain results in the gradual worsening of an individual’s cognitive functioning abilities (e.g., memory, decision-making) and eventually leads to damage to other parts of the brain responsible for performing everyday activities such as balance, movement, talking, swallowing and breathing.
As there are currently no treatments available to stop the progression of neurodegenerative diseases, researchers have begun to investigate the underlying causes of neurodegeneration in hopes of identifying novel treatments for neurodegenerative conditions such as Alzheimer’s disease. Rolipram — a selective phosphodiesterase-4 inhibitor and anti-inflammatory drug — may play a role in preventing dementia and reducing brain damage through its enhancement of proteasome (i.e., a cell’s waste disposal system) activity during the early stages of Alzheimer’s disease, according to a recent study published in the journal Nature Medicine.
Neurodegeneration in Alzheimer’s disease
Alzheimer’s disease is a neurodegenerative disease that involves the buildup of unusual proteins (protein beta-amyloid and tau) in and around neurons in the areas of the brain responsible for memory (e.g., hippocampus). Individuals who have Alzheimer’s disease gradually lose neurons and synapses in the cerebral cortex and other important brain areas (e.g., temporal lobe, parietal lobe, frontal cortex, cingulate gyrus), resulting in dramatic brain shrinkage in the advanced stages of the disease. It is the most common cause of dementia and affects as many as 10 to 20 percent of people over the age of 65, according to the Alzheimer’s Association (Page 14).
Alzheimer’s disease is characterized by the gradual declines in memory, language, problem solving and other cognitive skills, and eventually leads to a loss of ability to perform even the most basic everyday activities (e.g., breathing). Interestingly, certain genes that play a role in the development of Alzheimer’s disease, including tau, are physiologically involved in modulating brain plasticity (or the formation of new synapses or connections in the brain). In healthy people, proteins are formed of long amino acid chains in a particular three-dimensional conformation, but in people with Alzheimer’s disease, the beta-amyloid and tau proteins accumulate and become misfolded.
The accumulation of protein beta-amyloid (i.e., beta-amyloid plaques) outside neurons and an unusual form of the protein tau (i.e., tau tangles) inside neurons contribute to the development of Alzheimer’s disease. Beta-amyloid plaques interfere with neuronal communication at synapses, while tau tangles block the transport of nutrients and other essential molecules inside the neuron, both of which contribute to cell death.
Speeding up the brain’s waste disposal activity in Alzheimer’s disease
Karen E. Duff , Ph.D., professor of pathology and cell biology at Columbia University, and her colleagues investigated the effect of tau accumulation on proteasome (i.e., a hollow, cylindrical structure that chews up defective proteins into smaller pieces and recycles them into new proteins needed by a cell) activity in a genetically engineered mouse model of tauopathy. Tau is a structural protein that accumulates into clumps (i.e., tangles) in the brain cells of patients with Alzheimer’s disease and other neurodegenerative disorders.
The researchers discovered that as levels of abnormal tau increased, the proteasome activity slowed down. When the mice were treated with the drug rolipram during the early stages of tauopathy, proteasome activity increased, while tau accumulation decreased. By enhancing proteasome activity with rolipram during the early stages of Alzheimer’s disease, the researchers were able to reduce damage to the brain and prevent memory problems of mice (i.e., dementia). Importantly, rolipram worked exclusively when it was given during the early stages of neurodegeneration (when the mice were 4 months of age), and was not effective for treating mice at later stages of the disease.
For the first time, researchers have identified a drug (rolipram) that can effectively slow or prevent the progression of Alzheimer’s disease through its activation of proteasome activity. Duff and her colleagues plan to continue investigating the impact of tau and other disease-related proteins on proteasome activity using FDA-approved compounds or new molecules for drugs that work in a similar way to rolipram. “The proteasome system we are studying also degrades proteins associated with a number of other neurodegenerative diseases such as Parkinson’s, Huntington’s, frontotemporal degeneration and amyotrophic lateral sclerosis. We may be able to apply these findings to other disorders that accumulate proteins,” Duff said.
Current treatments available for Alzheimer’s disease
Many neurodegenerative diseases, including Alzheimer’s disease, involve progressive neuronal cell death. Currently, no treatments are available to cure neurodegeneration — rather, certain medications and treatments may be used to slow down the progression of the disease, while others boost the levels of neurotransmitters in the brain to help relieve symptoms and to help improve the patients’ quality of life.
Non-medication therapies, including music therapy and reminiscence therapy (i.e., therapy using photos and familiar items to help elicit recall), are also available for helping patients maintain or improve their cognitive function and overall quality of life. Although non-medication therapies may be beneficial for patients with Alzheimer’s disease, they do not slow down the progression of the disease.
Neurofeedback is considered to be an important tool for improving and strengthening cognitive function. One study found that neurofeedback has a positive effect on the cognitive performance of patients with Alzheimer’s disease. Patients with Alzheimer’s disease who received neurofeedback training demonstrated improvements in learning, memory and other cognitive functions (e.g., increased recognition and recall of information) and overall improvement in cognitive functioning compared to patients who were treated as usual.
The Sovereign Health Group recognizes the importance of improving cognitive function of adults and adolescents in treatment for substance abuse, mental illness and co-occurring disorders. Our evidence-based and individualized treatment programs include cognitive exercises and neurofeedback to help improve and strengthen our patients’ cognitive functioning and overall well-being. For more information about the neurofeedback or cognitive training programs offered at Sovereign Health, please contact our 24/7 helpline for further assistance.
About the author
Amanda Habermann is a writer for the Sovereign Health Group. A graduate of California Lutheran University, she received her M.S. in clinical psychology with an emphasis in psychiatric rehabilitation. She brings to the team her background in research, testing and assessment, diagnosis and recovery techniques. For more information and other inquiries about this article, contact the author at firstname.lastname@example.org.