Neurodegeneration refers to the progressive loss of structure and function of neurons, ultimately leading to their death. It underlies major disorders such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis, which share common cellular and molecular features despite affecting different brain regions and functions.

A central theme is protein misfolding and aggregation. Proteins such as amyloid beta, tau, alpha synuclein and TDP 43 can adopt abnormal conformations, form toxic oligomers and larger aggregates, and disrupt cellular homeostasis. These aggregates impair synaptic function, overwhelm protein quality control systems and trigger inflammatory responses.

Mitochondrial dysfunction and oxidative stress are tightly linked to this process. Damaged mitochondria generate excess reactive oxygen species that injure DNA, lipids and proteins. Impaired energy production further weakens neurons, which have exceptionally high metabolic demands. Failures in mitophagy and other autophagic pathways allow damaged organelles and proteins to accumulate.

Neuroinflammation is another key driver. Microglia and astrocytes, which normally support neurons and clear debris, can become chronically activated. This state promotes secretion of inflammatory mediators, exacerbating neuronal stress and death rather than resolving damage.

Genetic factors increase susceptibility by altering protein metabolism, vesicular trafficking, lipid homeostasis and innate immune signaling. However, age related changes remain the strongest risk factor, as repair mechanisms decline and cumulative damage grows.

Current research seeks to map the interplay among protein aggregation, mitochondrial failure, impaired clearance and inflammation. This systems level view aims to identify converging pathways that can be targeted therapeutically, with the goal of slowing or preventing neuron loss across multiple neurodegenerative diseases.