Life Sciences & Biotechnology
Title : | Gene Expression Profiling in Postmortem Tissue of Amyotrophic Lateral Sclerosis patients |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | "Dr. Saraswati Nashi, National Institute Of Mental Health And Neurosciences (NIMHANS), Bengaluru, Karnataka " |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | nandanashi@gmail.com |
Equipments : | SERVER |
Details
Executive Summary : | Amyotrophic lateral sclerosis (ALS) is a common motor neuron disease that causes degeneration of motor neurons in the primary motor cortex, brain stem, and spinal cord, leading to progressive paralysis of skeletal muscles and death due to respiratory failure. Most ALS cases are acquired spontaneously, while only 10%-15% are inherited. Several interdependent mechanisms induce motor neuron damage in both fALS and sALS, including excitotoxicity, aberrant RNA processing, altered axonal transport, protein aggregation, mitochondrial dysfunction, toxicity of nonneuronal (glial) cells, and oxidative stress. Inflammation and mitochondrial dysfunction are major pathomechanisms in motor neuron degeneration, with strong interconnections to oxidative stress cascades. These pathways form a vicious cycle that could be an initiator or mediator of motor neuron death. Studies have been conducted in SOD1 transgenic ALS animal and in vitro models, but few human autopsy studies on gene expression profiling could provide novel insights into the disease mechanisms in ALS. The study hypothesizes to identify altered expression of genetic pathways such as oxidative stress, neuroinflammation, and autophagy leading to motor neuron degeneration in samples of post-mortem cortex and spinal cord of ALS patients. The objectives are to investigate differential gene expression in oxidative stress, neuronal maintenance, neuroinflammation, and autophagy pathways in postmortem brain and spinal cord specimens of sporadic ALS patients and to identify rare genetic variants and their allele-specific gene expression in ALS patients compared to controls. |
Co-PI: | Prof. Atchayaram Nalini, National Institute Of Mental Health And Neurosciences (NIMHANS), Bengaluru, Karnataka-560029, Dr. Anita Mahadevan, National Institute Of Mental Health And Neurosciences (NIMHANS), Bengaluru, Karnataka-560029, Dr. Seena Vengalil, National Institute Of Mental Health And Neurosciences (NIMHANS), Bengaluru, Karnataka-560029, Dr. Chetan G K, National Institute Of Mental Health And Neurosciences (NIMHANS), Bengaluru, Karnataka-560029, Dr. Gautham Arunachal Udupi, National Institute Of Mental Health And Neurosciences (NIMHANS), Bengaluru, Karnataka-560029 |
Total Budget (INR): | 37,98,586 |
Organizations involved