cellular response to amyloid-beta

Definition

Target type: biologicalprocess

Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a amyloid-beta stimulus. [GO_REF:0000071, GOC:TermGenie, PMID:23555824]

Cellular response to amyloid-beta is a complex and multifaceted process involving multiple cellular pathways and signaling cascades. It begins with the accumulation of amyloid-beta (Aβ) peptides, which are toxic fragments of a larger protein called amyloid precursor protein (APP). Aβ aggregation initiates a cascade of events that lead to neuronal dysfunction and ultimately cell death.

The accumulation of Aβ triggers a variety of cellular responses, including:

**1. Activation of Microglia and Astrocytes:**
Microglia, the resident immune cells of the brain, and astrocytes, star-shaped glial cells, are activated by Aβ accumulation. Activated microglia release inflammatory mediators, such as cytokines and chemokines, leading to neuroinflammation. Astrocytes respond by increasing the expression of glial fibrillary acidic protein (GFAP) and releasing various factors, including growth factors and cytokines. Both microglia and astrocytes attempt to clear Aβ plaques through phagocytosis, but this process can become dysfunctional in the context of chronic Aβ accumulation.

**2. Mitochondrial Dysfunction:**
Aβ can disrupt mitochondrial function, leading to decreased ATP production and increased oxidative stress. This can lead to cell death by apoptosis or necrosis. Aβ can also directly interact with mitochondria, triggering the release of pro-apoptotic proteins, further contributing to cell death.

**3. Synaptic Dysfunction:**
Aβ accumulation disrupts synaptic plasticity, leading to impaired communication between neurons. This occurs through various mechanisms, including:
* **Interference with synaptic vesicle release:** Aβ can interfere with the release of neurotransmitters from presynaptic terminals.
* **Alterations in receptor function:** Aβ can bind to and modulate the function of various receptors, including glutamate receptors and acetylcholine receptors, disrupting synaptic transmission.
* **Changes in dendritic spine morphology:** Aβ can induce changes in the structure and function of dendritic spines, which are the sites of synaptic connections.

**4. Oxidative Stress:**
Aβ accumulation promotes the generation of reactive oxygen species (ROS), which can damage cellular components, including DNA, proteins, and lipids. This oxidative stress contributes to neuronal damage and death.

**5. Cell Death:**
Aβ accumulation triggers various cell death pathways, including apoptosis and necrosis. Apoptosis is a programmed cell death process, while necrosis is a form of uncontrolled cell death.

**6. Immune System Involvement:**
The immune system plays a complex role in the response to Aβ. While the brain's immune cells (microglia) attempt to clear Aβ plaques, chronic inflammation can contribute to neuronal damage.

**7. Tau Hyperphosphorylation:**
Aβ accumulation can contribute to the hyperphosphorylation of tau protein, a microtubule-associated protein. Hyperphosphorylated tau aggregates into neurofibrillary tangles, which are a hallmark of Alzheimer's disease.

In summary, cellular response to amyloid-beta is a complex and multifactorial process that involves a cascade of events leading to neuronal dysfunction and cell death. This process is intricately linked to neuroinflammation, mitochondrial dysfunction, synaptic dysfunction, oxidative stress, and various cell death pathways. The understanding of these mechanisms is crucial for developing effective therapeutic strategies against Alzheimer's disease.'
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Proteins (32)

Compounds (1,141)